Cell-mediated immunity is a requirement for recognition and elimination of cells and for prevention or treatment of a variety of diseases. Therefore, the development of a product potentially active in increasing immunity involves its testing in assays specific for cell-mediated immunity. The effectiveness of a single administration of levamisole was demonstrated in the rejection of isografts in a male to female C57BL/6 system, and on the enhancement of levels of the delayed type hypersensitivity (DTH) to sheep red cells (SRBC). Indeed, in five on nine tests, an injection of 25 mg/kg of levamisole to female recipients either on the day of grafting or 7 days after grafting resulted in a RT50% rejection time of 25 days, compared with 46 days in untreated controls. Levamisole administered at the time of immunization with various doses of SRBC elicited earlier, higher and more sustained DTH levels than in untreated controls. Such induction of T-cell activation was accompanied by a switch on anti-SRBC antibodies from IgM to IgG. These findings confirm and extend data evidencing the ability of levamisole to recruit and activate T cells for an increased or restored cell-mediated immunity.