We studied the effects of testosterone substitution on serum concentrations of lipids, lipoproteins, apoproteins and on the activity of hepatic lipase (HL) and lipoprotein lipase (LPL) in postheparin plasma and on the activity of LPL in adipose tissue (AT-LPL) in 13 male hypopituitary patients. The activities of LPL and HL in postheparin plasma were markedly increased by 1 week after a testosterone enanthate injection (P less than 0.001). The HL activity remained elevated (P less than 0.05) after 1 month's treatment, but the LPL activity declined to presubstitution levels. The prolonged substitution decreased serum apoproteins A-I and A-II (P less than 0.05). The changes of apo A-I and A-II correlated inversely with those of the free testosterone index (FTI) (r = -0.74, r = -0.67, P less than 0.05). Serum HDL-cholesterol level decreased slightly by 1 week and it correlated inversely with the increase in testosterone and the FTI (r = -0.67, r = -0.85, P less than 0.05). The results suggest that testosterone increases the activity of both lipolytic enzymes in postheparin plasma. The effect on HL appears to be more persistent than that on LPL. The data support a role for androgens in the regulation of serum lipoprotein and HDL-cholesterol levels.