Peritoneal as well as peripheral blood, but not spleen macrophages inhibit natural killer (NK) cell activity directed against adherent growing target cells. Inhibition was observed with macrophages (Mø): spleen cell ratios as low as 0.01:1. It was independent from the activation status of Mø and was not MHC restricted. With respect to the mechanism, cell contact was essential. A cold target mechanism, reflected by some binding, but not killing, of NK cells by Mø was of minor influence. Spontaneously by Mø released soluble mediators could be excluded, nor was any soluble mediator released upon contact of Mø with spleen cells, but NK activity could be partly inhibited by supernatants from cocultures of Mø with adherent growing target cells.