Heavy metal treatment (2 x 1 mg/kg per day) for 3, 5, and 7 days resulted in progressive augmentation in the incorporation of [14C]thymidine into hepatic DNA. In contrast with the observed enhancement in DNA synthesis, cadmium exposure tended to produce a decrease in the activity of hepatic ornithine decarboxylase (EC 22.214.171.124) at 1, 3, or 5 days with the lowest (34% of control values) enzymic activity seen after 7 days. A similar reduction in the activity of S adenosylmethionine decarboxylase (EC 126.96.36.199) was observed in livers of rats treated with cadmium for 1-7 days. Subacute exposure to cadmium significantly lowered the hepatic levels of spermidine and spermine whereas the endogenous concentration of putrescine remained unaltered. In addition to the observed effects on the biosynthesis of polyamines and DNA, heavy metal treatment produced stimulation of the hepatic adenylate cyclase (EC 188.8.131.52) cyclic AMP system. Significant increases in the activity of hepatic adenylate cyclase and endogenous cyclic AMP levels were detected as early as 1 day and the observed alterations persisted during the entire 1 wk period of cadmium exposure. The depression in polyamine formation was accompanied by enhanced DNA biosynthesis as well as stimulation in the adenylate cyclase cyclic AMP system of rat liver.