Leucogenenol, a compound isolated from the metabolic products of Penicillium gilmanii by Rice (1) and from human and bovine liver by Rice and Shaikh ( 2 ) and indicated by degradation studies to be 2-( 1, 2-dihydroxy-3-methyl-5-oxo-cyclohexyl) -3 , 1 1dihydroxy-11 -(hydroxymethyl) -9-methyl-loxa-5-azaspiro [ 5,s ] undeca-2,4-diene-7-one (3), induces a leukocytosis when it is injected intravenously or intraperitoneally into rabbits (4) , dogs, mice, or monkeys (5,6).Injection of leucogenenol into animals is followed by a relative increase in the number of myeloblasts in the bone marrow and lymphoblasts in the spleen ( 5 , 6), suggesting that leucogenenol stimulates the rate of replication of these cells from their respective precursors. The stimulatory action of Ieucogenenol on lymphoid cells is also indicated by the finding that leucogenenol decreases the latent period required for antibody production in sublethally X-radiated mice (7). The addition of leucogenenol to a culture of human lymphoblastoid or mouse leukemic cells increases their respiratory quotient and their rate of replication (8), suggesting that leucogenenol acts directly on the blood cells of animals.I t was of interest, therefore, to establish whether or not leucogenenol acted specifically on one or more of the progenitors to the circulating blood cell. Patt and Maloney demonstrated (9) that tritiated thymidine is first incorporated in the blast forms of myeloid and erythroid cells and then is carried through the series of myeloid and erythroid cells to appear in the corresponding circulat-ing cells approximately 24 hr later. It appeared therefore that studies of the effect of leucogenenol on the time and intensity of the labeling of bone marrow blood cells with tri t ia ted thymidine should indicate whether or not leucogenenol acted on one or more types of myeloid and erythroid blood cells. SimilarIy it might be possible to establish whether or not leucogenenol acted on one or more types of lymphoid cells. Accordingly rats were injected with tritiated thymidine and leucogenenol and the type and number of labeled blood cells in their bone marrow, spleen, and peripheral circulation compared by standard autoradiographic techniques (10-12) with the number of corresponding labeled cells in the bone marrow, spleen, and peripheral circulation of rats that were injected with tritiated thymidine alone.Materials and Methods. Each of 60 rats (Wistar, approx. 250 g) was injected intraperitoneally with tritiated thymidine2 (1 pCi/g of body wt). At approximately the same time 30 of the rats were injected intravenously through the tail vein with 0.02 pg of the calcium salt of leucogenenol dissolved in 0.2 ml of pyrogen-free isotonic saline. At intervals of 6, 12, 24, 48, and 96 hr thereafter a sample of blood was obtained from the tail vein of each rat, diluted in the usual manner in a Trenner pipet and the number of leukocytes was determined by means of a hemocytometer. Counts made in duplicate differed by less than 10%. Smears of blood for differential coun...