Changes in the adrenal weight, adrenal 5-ene-3 beta-hydroxysteroid dehydrogenase (5-ene-3 beta-HSD) activity and serum levels of corticosterone were observed in male wistar rats after the treatment of lithium chloride in the doses of 100, 200 and 400 micrograms/100 g of body weight/day for 7, 14 and 21 days. The experiments indicate that 200 and 400 micrograms/100 g.b.w. administered for 14 and 21 days caused a significant stimulation in the activities of adrenal 5-ene-3 beta-HSD along with elevation of adrenal weights and serum levels of corticosterone. 100 micrograms of lithium chloride was not able to modulate the adrenal activity. Moreover, plasma levels of lithium remain in therapeutic range in this experiment at the doses of 200 and 400 micrograms/100 g body weight. Therefore, our data suggest that lithium can alter the adrenal activity within its therapeutic range according to the duration of treatment.