Cocaine acts directly on lymphoid cells and indirectly modulates the immune response by affecting the level of neuroendocrine hormones. In vitro, very high concentrations of cocaine inhibit different immune responses, while plasma levels following cocaine use have no effect. The results of the few published in vivo studies are contradictory, showing stimulatory, suppressive or no effect on lymphoid cells. The indirect effects of cocaine on the immune system could be mediated by ACTH, beta-endorphin and corticosterone. Anorectic effect associated with nutritional deficiencies of drug users could additionally affect the immune response by cocaine.