To identify and measure the spontaneous cell-mediated cytotoxicity of natural killer cells, we used the lysis of an established lymphoblastoid cell line as target in a 4-hr 51Cr-release assay. Mononuclear cell suspensions of the peripheral blood of thirty-four patients with Crohn's disease (group CD), eleven patients with inflammatory bowel disease other than CD or ulcerative colitis (group D) and forty-five healthy subjects matched for both age and sex with the patients were studied. Depletion of phagocytic, plastic-adherent cells ('purified suspensions') led to a significant increase of the natural killer cell activity as compared with unseparated suspensions. This was seen to occur in all groups. In CD patients the natural killer cell activity was significantly below normal levels in both unseparated and 'purified' suspensions. This was independent of disease duration. In 'purified' suspensions the natural killer cell activity was inversely related to the disease activity. In group D the natural cytotoxicity was significantly lower in unseparated suspensions than that in healthy controls. In 'purified' suspensions it was still slightly lower than in healthy controls.