Methimazole (MM), an antithyroid drug, was examined for its ability to modulate immune functions. The increase in [3H]thymidine incorporation in plant mitogen-stimulated lymphocytes and augmentation of NK cell activity by MM were used as a measure of the immunomodulatory activity of MM. The results demonstrated that lymphocytes from 5 different donors had a mean increase of 632% of [3H]thymidine incorporation in the presence of MM at a concentration of 114.2 micrograms/ml (P less than 0.005). Lymphocyte response to PHA, Con A or PWM was potentiated by 27 to 482% in the presence of MM. The MM mediated increase in lymphocyte proliferation was more obvious in cases where the mitogenic stimulation was low. Lymphocyte cytotoxicity to both K562 cells and malignant B cells was also augmented when lymphocytes were cultured in the presence of MM. A maximal effect was observed when lymphocytes were treated with a concentration of 20 micrograms/ml of MM for 12-16 hr. Maximum augmentation was usually exerted when the NK cell activity of cultured lymphocytes was low. This was particularly seen with lymphocyte from cultured B cell leukemia (3163).