Lymphocytes from control donors and from cancer patients have been tested for antitumor, cell-mediated immunity against various melanoma and breast cancer target cell cultures with a microcytotoxicity assay. Control lymphocytes inhibited growth of target cells with high frequency, particularly with cell line, as opposed to short-term, cultures. Inhibition was not found for all target cells tested at a given time with a single preparation of lymphocytes. Sequential studies over a 2-year period with lymphocytes from the same control donors showed fluctuations of inhibition against the same target cells. With serial passage, the target cells also changed in their susceptibility to destruction by control lymphocytes. Lymphocytes from melanoma patients were more inhibitory than control lymphocytes for one melanoma target cell culture but not for two other melanoma cultures. Significant inhibition by lymphocytes from melanoma patients was not seen against two cultures derived from breast cancer patients. Lymphocytes from breast cancer patients were more inhibitory than control lymphocytes for 4 of 5 breast cancer cultures and they did not inhibit two melanoma cultures. Significantly specific inhibition was seen with short-term, but not cell line, breast cultures. The over-all data show specificity for target cells of the appropriate histological type. However, the high and inconstant reactivity of control lymphocytes in this assay suggests that nonspecific inhibition of tumor target cells by patient lymphocytes is found in many experiments. It is concluded that the microcytotoxicity assay is not suitable for clinical studies, since sequential data obtained in individual patients are difficult to interpret.