Rats after adrenalectomy-testectomy showed a gradual increase in diencephalon 3-oxo-5α-steroid:(acceptor)Δ⁴-oxidoreductase (5α-reductase) activity for 3 days. The activity then returned near to the normal range on the 4th postoperative day. When rats were given testosterone propionate (TP) 3 days after adrenalectomy-testectomy, diencephalon 5α-reductase activity returned to the preoperative range 2hr after TP administration. Diencephalon 5α-reductase activity showed a highly significant increase (p<0.01) after a single administration of carbamazepine, reserpine, diazepam, phenytoin, phenobarbital or disulfiram. A significant increase (p<0.05) was also found after a single administration of methylphenidate, caffeine or methamphetamine. Plasma testosterone decreased concurrently after administration of all these agents, except diazepam. Diencephalon enzyme activity decreased significantly after repeated disulfiram administrations (p<0.01) but increased significantly after methamphetamine administrations (p<0.05). Plasma testosterone showed a tendency to decrease after repeated methamphetamine administrations but tended to increase after repeated disulfiram administrations.