Daily intraperitoneal injection of cadmium chloride (0.25 or 1 mg/kg) to rats for 45 days significantly elevated the endogenous levels of cyclic AMP (cAMP) in hepatic tissue. However, the cAMP binding to hepatic protein kinase was decreased following cadmium administration, as was the kinase activity ratio. Although both doses of cadmium produced slight alterations in the cAMP-independent form of hepatic protein kinase, only the 1.0 mg/kg dose significantly depressed (24%) the activity of the cAMP-dependent enzyme. In contrast to liver, chronic exposure to cadmium significantly reduced the endogenous cAMP levels in kidney cortex. Although treatment with the lower dose (0.25 mg/kg) failed to alter either the cAMP-binding capacity of the renal enzyme or the kinase activity ratio, the higher dose (1 mg/kg) of cadmium did cause a significant increase in both parameters. In addition, cadmium treatment produced a significant decrease in both the cAMP-dependent and the independent forms of protein kinase in kidney cortex. Data suggest that the concentration of cAMP as well as its interaction with cAMP-dependent and independent forms of protein kinase, are altered in both kidney and liver following the prolonged exposure to cadmium.