Delta-9-tetrahydrocannabinol (THC), the major psychoactive component of marijuana, can suppress the immune response, both in vitro and in vivo. In the present study, THC was found to either up-regulate or down-regulate lymphocytes depending on the method of stimulation. When the mitogens concanavalin A (Con A) or phytohemagglutinin (PHA) were used to stimulate THC-treated splenocytes, a down-regulation of lymphocyte proliferation occurred, which reflected lower T-cell numbers in general and Ly2 positive cells specifically. When splenocytes were stimulated directly by using anti-CD3 antibody it was found that low concentrations of THC enhanced lymphocyte proliferation, T-cell numbers in general, and Ly2 cells specifically. These results emphasize that THC can either enhance or suppress aspects of the immune response, depending on the specific immune stimulants used and the specific parameter of immunity measured.