Compounds with known psychotropic properties were tested for activity in murine i.p. L1210 [mouse] leukemia and B16 [mouse] melanoma in a protocol designed to obtain leads for new antitumor agents which might also possess CNS antitumor properties. Barbiturates and hallucinogenic compounds were the only compound types deliberately excluded. Representatives from most of the other known CNS agent classes were included among the 297 psychotropic drugs evaluated. Sixteen of these agents were reproducibly active against the L1210 tumor system with T/C [therapy to control ratio] values of 125-150%. Phenothiazines such as fluphenazine and butyrophenones such as triperidol were prominent among the confirmed active structural types. Dopamine, a .beta.-phenethylamine neurotransmitter, was active. While reproducible B16 melanoma activity was not observed among the psychotropic drugs, most of the L1210 confirmed active agents were effective against the i.p. P388 tumor model and also were active in vitro against KB cells. Ic L1210 activity was not observed among the few compounds chosen for testing in that tumor system. The yield of i.p. L1210 confirmed actives from this group of psychotropic agents was 18 times that which would have been expected from the random screening of compounds.