The effect of levamisole upon cell-mediated immunity was investigated using the oxazolone-induced contact sensitivity response in immunosuppressed and nonimmunosuppressed C57Bl male mice. Mice were sensitized to oxazolone on day 0, and where appropriate, methotrexate (1 mg/kg, p.o.) was administered on days 1 and 2. On day 3, levamisole (5--50 mg/kg, p.o., base) was administered. One hour later, the animals were challenged with oxazolone on the left hindpaw. Twenty-four hours after challenge, the resulting edema was read plethysmographically. Levamisole, in the absence of immunosuppression, had no significant effect upon the oxazolone response whereas, in the face of immunosuppression, restoration of oxazolone responsiveness was observed. These results were suggested to be due to (1) the ability of levamisole to stimulate opposing suppressor and effector components of the oxazolone response coupled with (2) an apparent alteration of suppressor influence by methotrexate allowing levamisole to enhance an unencumbered effector cell population.