Indocyanine green is a water-soluble tricarbocyanine dye developed by Brooker and introduced by Fox et aZ.(l,2) for measurement of cardiac output by the indicator dilution technic. For this purpose its absorption spectrum and protein-binding characteristics ( 1 ) are ideally suited. The results of the present investigation indicate that the dye may also be of great value in study of hepatic function.Methods. All studies were conducted on 2 trained unanesthetized female dogs weighing 18.9 and 2 2 . 0 kg. Several months previously each had undergone splenectomy, cholecystectomy, and preparation of a permanent duodenal fistula using the device described by Thomas(3), which permitted access to the common bile duct. The dogs remained in good health, and hepatic function, as judged by repeated measurements of sulfobromophthalein (BSP) transfer maximum ( 4 ) , continued unimpaired. At the time of each study an olive-tipped ureteral catheter (5 or 6 Fr.) was inserted through the ampulla of Vater and advanced about 5 to 6 cm into the common bile duct. The dogs were then placed upright in a sling and bile was collected by gravity or, when it was particularly viscous, by gentle *This work was made possible by grants from the New York Heart Assn. and the Department of the Army (Contract DA-49-007-MD-205). t MarkIe Scholar in Medical Science. $ Rockefeller Travelling Fellow in Medicine,aspiration with a tuberculin syringe. Intravenous injections were given through a polyethylene catheter introduced through a large bore needle in a vein of the foreleg and advanced to the region of the right atrium.Indocyanine green$ was made up to 2 5 0 mg% in distilled water for injections. In one study a continuous infusion of the dye was given. This was prepared by mixing 2 4 ml of SO0 mg% indocyanine green with 51 ml of normal saline and 5 ml of dog plasma. (Indocyanine green is unstable on standing in aqueous solution, and the presence of plasma was found empirically to retard its breakdown.) Concentration of indocyanine green in plasma was measured in a Beckman DU spectrophotometer at 8 1 0 mp after 1 1 -fold dilution with normal saline. Concentration standards for this determination were also prepared in dog plasma. (Dilute aqueous standards are unsatisfactory because of marked instability.) Bile samples were diluted 25 to 100 times with water. One ml of diluted bile was then added to 1 ml of dog plasma and 9 ml of normal saline and the absorption measured at 8 1 0 mp. Although the dye is quite stable in bile even when diluted, the addition of plasma, for reasons not apparent, was necessary for full color development. BSP concentrations 0 Kindly supplied as "Cardio-Green" by Hynson, Westcott and Dunning, Inc., Baltimore, Md., through the courtesy of Dr.

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SUMMARY1. Leucocyte pyrogen has been injected bilaterally into various parts of the rabbit brain. It caused fever when injected into the pre-optic area and the anterior hypothalamus, but not when injected into the posterior hypothalamus, the mid-brain, the pons, the cerebellum or the cerebral cortex.2. The mean time which elapsed between a leucocyte pyrogen injection into the anterior hypothalamus and the onset of fever was 7-8 min. For similar injections of bacterial pyrogen the time lag was 24-8 min. The mean time lag between bilateral injections of noradrenaline into the anterior hypothalamus and the onset of fever was 7-4 min.3. The amount of leucocyte pyrogen required to cause fever when injected into the anterior hypothalamus was less than 1/100 of that required to cause a similar fever on intravenous injection. The quantity of bacterial pyrogen injected into the hypothalamus was of the same order as that which would cause a similar fever on intravenous injection.4. Control injections of saline, plasma, cerebrospinal fluid, heated leucocyte pyrogen and red cells into the anterior hypothalamus did not cause fever. 5. After attempts to deplete the hypothalamus of its monoamine stores by intraventricular injections of reserpine, the rabbit had fever as a result of an intravenous injection of bacterial pyrogen.6. We conclude that the anterior hypothalamus and the pre-optic area are sites at which leucocyte pyrogen acts to cause fever in the rabbit. The mechanism of this febrile response is not clear, but it appears that part, at least, of the response could be mediated by a mechanism other than release of noradrenaline or failure to release 5-HT.