The effect of a 550-kcal mixed meal and of an intravenous injection of pentagastrin (0.06 microgram/kg body wt) upon peripheral blood serotonin concentrations has been compared in 10 carcinoid patients with hepatic metastases and healthy subjects. The fasting concentrations of blood serotonin in the patients (range 790-4500 ng/ml) were elevated compared with healthy subjects (range 71-310 ng/ml; n = 15). Urinary output of 5-hydroxyindole acetic acid was elevated in 8 patients but was in the healthy range for 2 patients. The healthy subjects (n = 9) responded to food with an increase in blood serotonin (maximum rise over mean basal of 32% +/- 4%) that was significant at 60, 75, 90, and 105 min postcibal. All carcinoid patients responded to food with a comparable (25% +/- 11% over basal) rise in serotonin but the pattern of release was erratic. All patients with tumor metastases exhibited symptoms of the carcinoid flush after eating, but there was no correlation between occurrence and severity of the flush and occurrence and magnitude of the rise in serotonin. Intravenous pentagastrin evoked a flush in all carcinoid patients, but there was no significant increase in peripheral blood serotonin either in the patients or in healthy subjects.