The effects of cancer patient and normal donor serum samples on the reactivity of patient and normal lymphocytes against both normal and malignant target cells were studied in microcytotoxicity assays. There were 17 of 140 cancer patient serum samples and 7 of 116 normal donor lymphocyte samples that selectively increased the growth of target cells in the presence of lymphocytes. This effect was most often noted with cancer patient serum against cultured tumor cells, but the effect was also noted against fibroblasts and with normal serum against both fibroblasts and tumor cells. Of 140 cancer-patient serum samples, 11 selectively decreased target cell survival in the presence of lymphocytes compared to medium and compared to other serum samples. In the absence of lymphocytes these serum samples were nontoxic. The effect was not observed with any of the normal serum samples studied. The lymphocyte-dependent serum toxicity appeared to be selectively directed against tumor target cells.