The histamine-2 receptor antagonist cimetidine (10(-5)M) and the prostaglandin synthesis inhibitor indomethacin (10(-8)M) augmented natural killer cell activity in the majority of healthy controls and patients with advanced melanoma and in a lower frequency of patients with colorectal carcinoma. Antibody-dependent cellular cytotoxicity was increased in most melanoma patients but in a lower proportion of patients with colorectal cancer. Compared with the effect of interferon the augmentation of NK- and K-cell activities was small in most patients. Cimetidine was also demonstrated to bring about a further increase in the interferon-induced NK activation of peripheral blood mononuclear cells from a majority of healthy donors and patients with melanoma. Furthermore, cimetidine augmented the interferon-induced K-cell activation of peripheral blood mononuclear cells from most patients with melanoma and colorectal cancer.