Two different molecular forms of cholecystokinin (CCK) were studied with respect to their modulatory effect on non-MHC restricted or natural killer (NK) cell cytotoxicity. NK activity of peripheral blood mononuclear cells was found to be hardly affected by co-incubation with either CCK-8 or CCK-33 within a physiological concentration range against K-562 or Caco-2 tumour target cells. NK activity by lamina propria mononuclear cells isolated from histologically normal intestinal mucosa was found to be enhanced dose-dependently by incubation with CCK-8 in the 4-h assay against K-562, but not in the prolonged 18-h assay or against Caco-2 targets. In contrast, CCK-8 showed a tendency to inhibit NK activity in the prolonged 18-h assay against K-562; however, these alterations were not found to be statistically significant. CCK-33 was not found to modulate the NK activity of lamina propria mononuclear cells. It is suggested that NK activity by lamina propria mononuclear cells may be stimulated preferentially by CCK-8 because this molecular form of CCK in particular predominates in the nervous tissue of the intestinal mucosa.