In order to evaluate the effect of biological response modifiers on NK- and NK-like activity, interferons were tested in the single cell cytotoxicity assay (SCCA) with various effector/target combinations. alpha Interferon (IFN-alpha) significantly augmented the cytolysis of K 562 in vitro by non-adherent peripheral blood lymphocytes of normal donors without any influence on the binding capacity. Similarly, in vivo, the intraperitoneal administration of gamma Interferon (IFN-gamma) to patients with ovarian carcinomas resulted in a significant increase in the autologous cytotoxicity in the ascitic compartment. Nevertheless the autologous total killer activity was not improved owing to the countercurrent trend of the conjugate formation. Moreover, we detected a discrepancy in the development of the autologous and allogenic parameters as a result of the strong effects of the peritumorally administered IFN on the effusion tumour cells. In order to investigate the role of epidermal NK-like activity in immunosurveillance we tested epidermal cells as effectors against K 562 and the long-term cultured melanoma cell line RIMA. The SCCA detected the ability of conjugate formation without any cytotoxicity, augmentable significantly and in a dose-related manner by IFN-gamma, as the only one of ten tested biological response modifiers.