Serotonin uptake by platelets was determined in 11 patients suffering from carcinoma of the pancreas, eleven patients hospitalized for chronic physical disease, 19 patients suffering from major depression unipolar type, and 19 healthy volunteers. The Vmax values of serotonin uptake were significantly lower in patients suffering from carcinoma of the pancreas (F = 18.6, df = 28, Ρ < 0.001) and chronic physical disease (F = 21.3, df = 28, Ρ < 0.0001) than in healthy volunteers. The Vmax values of the depressed patients were also significantly lower (F = 4.27, df = 36, Ρ < 0.05) than those in the control group. No difference was found between the carcinomatous and the chronically ill patients. Km values of serotonin uptake by platelets were significantly decreased in both groups of patients with organic disease (F = 5.91, df = 28, Ρ < 0.025; F = 4.44, df = 28, Ρ < 0.045 respectively) as compared to the control group, but were similar in the depressed and the control groups (F = 0.42, df = 20, P = 0.52). Since the patients with chronic disease were chronically medicated, the decreased serotonin uptake may not be disease-dependent but rather associated with medication. However, the carcinomatous patients were drug-free and in this group the decreased uptake and serotonin transporter hypersensitivity may have been disease-dependent. These results suggest the involvement of the presynaptic serotonergic system in the susceptibility of pancreatic carcinomatous patients to prodromal depression.