This report describes the response of normal human T cells to stimulation in vitro in the presence of nano-micromolar concentrations of cocaethylene. Thymidine incorporation by concanavalin A-stimulated peripheral blood mononuclear cells was generally blunted by cocaethylene, albeit to different degrees depending upon the donor tested. The formation of concanavalin A-induced blast cells was decreased by increasing concentrations of cocaethylene. The production of interleukin-2 was also blunted in a dose-dependent fashion by cocaethylene, and this outcome was more consistently observed in stimulated peripheral blood mononuclear cells, compared to unseparated whole blood preparations. An inverse dose dependence was obtained in relation to the response of blast cells to recombinant human interleukin-2 in the presence of cocaethylene. These lines of evidence, taken together with our preliminary studies aimed at testing the effect of cocaethylene on the expression of certain membrane markers of activation (i.e., interleukin-2 receptor, transferrin receptor, serine aminopeptidase IV) and the expression of the proliferating cell nuclear antigen (cyclin PCNA), suggest that cocaethylene modulates relatively early events following T cell stimulation probably related to the interleukin-2 system.