The effects of BCG vaccine on immunologic function were assessed in 4 patients with malignant melanoma. Cell-associated immune function was quantitatively measured in vitro by the incorporation of 3H-thymidine into frozen-stored lymphocytes in response to specific antigens (both related and unrelated to BCG), allogeneic lymphocytes, and phytohemagglutinin (PHA). In vivo, cell-mediated immunity was determined by delayed hypersensitivity skin reactions to various antigens. Serum IgG, IgM, IgA, and C'3 (complement) levels were quantitated. BCG administration significantly augmented antigen-induced incorporation of 3H-thymidine in 3 patients, with little or no effect on responses to allogeneic lymphocytes or PHA. BCG selectively increased serum IgG levels in the same 3 patients. IgA, IgM, or complement levels were not enhanced. All patients converted their purified protein derivative (PPD) skin-test reactivity from negative to positive during therapy, and in 2 patients candida skin reactivity appeared. These effects on cell-associated immune functions, immunoglobulin, complement levels, and in vivo-delayed hypersensitivity were consistent with the hypothesis that BCG primarily augments host responsiveness to antigens to which the host has previously been exposed. No effect on the primary immune response was detected. The 1 patient who did not respond to BCG by either cell-associated humoral immunologic enhancement had metastatic disease before initiation of study, which then rapidly progressed. Clinically, 2 of the 3 patients reacting immunologically, in addition to the 1 patient who failed to respond, developed progressive metastatic disease during therapy. One patient continues to respond immunologically and remains Free of progressive disease.