Cocaine abuse is known to be associated with suppression of the immune system. In this experiment, animals treated with cocaine (CC) in their drinking water (200 mg/L) for 10 days resulted in a significant decrease in thymus weight in HSD-NDA male Swiss mice. A subsequent in-vitro experiment was designed to investigate the direct effect of cocaine and other dopaminergic agents on thymocyte proliferation. Thymus glands were aseptically removed from mice and thymocytes were isolated and then incubated in microtiter plates with various concentrations (10[-8]-10[-4] M) of CC, apomorphine (AM), haloperidol (HP), dopamine (DA) and epinephrine (EN) for 18 hrs. The results revealed that cocaine inhibits [3H]-thymidine uptake into DNA in a dose-dependent manner. Apomorphine, haloperidol and dopamine also exhibited a similar dose dependent inhibition of thymocyte proliferation. The IC25s for DNA synthesis inhibition were 8.2 x 10(-6) M, 4.3 x 10(-7) M, 2.5 x 10(-7) M, and 1.1 x 10(-7) M for CC, HP, DA and AM, respectively. EN was found not to have any significant effect on DNA synthesis. The results suggest that thymus gland atrophy, associated with use of CC may be related to the inhibition of thymocyte proliferation.