In a study to determine the effect of saturation of fats on their ability to stimulate cholecystokinin (CCK) release six normal volunteers ate five test meals containing different fats with intervals of 1 week. Plasma CCK levels were measured by a specific radioimmunoassay and the gallbladder volume was calculated from ultrasound measurements. The sodium salt of the monounsaturated fatty acid oleic acid (3.5 g) produced a significantly greater integrated CCK response than that of the saturated fatty acid stearic acid (mean [SEM] 103 [41] vs 8[41] pmol.l-1.min). The gallbladder contracted to 42 (3)% of its initial volume after oleate but remained at 89 (8)% of its initial volume after stearate. Integrated CCK responses to dietary triglycerides (30 g) also differed significantly according to the degree of saturation--277 (58) pmol.l-1.min after corn oil (predominantly diunsaturated), 143 (14) pmol.l-1.min after olive oil (predominantly monounsaturated), and 44 (12) pmol.l-1.min after suet (predominantly saturated). The finding that unsaturated fats are stronger stimulants of CCK release than saturated fats may explain the promotion of pancreatic carcinogenesis in rats by unsaturated but not saturated fats and may support the role of CCK in this effect.