Summary: In this study, the cisternal CSF contents of lactate and glucose were sequentially measured in free moving rats that had been administered probenecid, 200 mg/kg-I, drug diluent, or no injections. In animals re ceiving either no injections or injections of drug diluent, CSF lactate and glucose were constant over a 6-h period (93-106% of control), whereas rats receiving probenecid showed increased lactate at 1 and 2 h (170 and 125% con trol, respectively) and increased glucose at 1, 2, and 3 h (169, 141 and 129% control, respectively). Cerebral cortex content of energy metabolites and lactate and blood lactate levels were statistically unaltered at 0.5-6 h exposure to probenecid, whereas cerebral and blood glu cose contents were increased after I and 2 h exposure to probenecid. Rats exposed to 5% O2 and probenecid for Probenecid [P-(dipropylsulfamoyl) benzoic acid] competitively inhibits the transport of 5-hydroxyin dole acetic acid (5-HIAA) and homo vanillic acid (HVA) from brain to blood (Guldberg et aI., 1966;Korf and Van Praag, 1971; Faull et aI., 1981). Avail able kinetic data suggest that the predominant sites for this organic acid transport system are the choroid plexus (Forn, 1972) and cortical-spinal subarachnoid space and their respective vascular structures (Wolfson et aI., 1974; Burns et aI., 1976; Van Der Poel et aI., 1977). Pardridge et ai. (1975) have presented data that indicates that probenecid also competitively inhibits the capillary endothelial monocarboxylic acid carrier. This has been con firmed by Yuwiler et al. (1982), who demonstrated that probenecid inhibits the uptake of short-chain Received April 7, 1986; revised September 16, 1986. 118 0.5 h showed a statistically higher CSF lactate at 0.5 and 1.5 h reoxygenation (169 and 168% control, respectively). A similar effect was also seen in rats exposed to 5% O2 and the 5-hydroxyindoleacetic acid (5-HIAA) transport inhibitor Na divalproate. The results suggested that the increase in CSF glucose was secondary to a probenecid induced elevation of blood glucose, whereas the increase in CSF lactate seemed to be secondary to a reduced rate of efflux of lactate from the CSF. It is suggested that it may be possible to increase the CSF lactate content by mechanisms that are independent of direct effects on the processes of cerebral energy metabolism. Key Words: Probenecid-CSF lactate-Cerebral energy metabolism -Blood-brain transport.monocarboxylic acids, such as lactate and proprio nate, from blood to brain. As the steady-state efflux rate of lactate from brain is estimated to be about 3 times that of influx (Pardridge et aI., 1975), it is pos sible to postulate on the basis of the above data that probenecid administration could result in an in crease in the lactate content of the cerebrospinal (CSF) and extracellular fluid of the brain. The ob jective of the present study was to test this hy pothesis by direct measurement of the cisternal CSF lactate content of rats administered proben ecid. In addition, the cisternal CSF glucose conten...