Human peripheral blood lymphocytes (PBL) were found to be highly cytotoxic to a human malignant melanoma target cell line after the PBL were cultured in medium supplemented with 20% fetal bovine serum (FBS). The effector cells had surface markers similar to those of non-cultured NK effectors against melanoma targets. Both NK (without culture) and the culture-induced cytotoxic effectors had Fc gamma receptors, lacked Fc mu receptors and were either heterogeneous for E receptors or had low-affinity E receptors. Cells required to generate the FBS response were sensitive to anti-T serum plus complement, passed through a nylon-fiber column, formed E rosettes, but lacked detectable receptors for the Fc portions of either IgG or IgM. These results suggest that events causing activation of T cells such as culture of PBL in FBS-containing medium, result in the augmentation of NK activity.