Preliminary data on the existence of a plasma pool of serotonin (5HT) in human blood has been confirmed in a descriptive study of two distinctive pools of 5HT (plasma and platelet), and its metabolite 5-hydroxyindoleacetic acid (5HIAA), in the blood of 175 healthy individuals. Plasma 5HT (0.93 +/- 0.67 ng/mL, X +/- S.D.) shows a significant but low correlation with platelet 5HT (711 +/- 319 ng/10(9) platelets) (r=0.29, p less than 0.001). Diastolic blood pressure correlated significantly with plasma 5HT (r=0.51, p less than 0.05) and whole blood 5HT (r=0.52, p less than 0.05) in older individuals (50-65 years) but not in the whole group (r=0.052, n.s.). Differences between sexes include plasma 5HT, whole blood 5HT (both higher in women) and plasma 5HIAA (lower in women) and may reflect a differential whole body 5HT function. The effect of meal consumption and a peripheral 5HT synthesis inhibitor (carbidopa) in four human subjects has also been tested. Carbidopa (0.7 mg/kg) significantly lowers the plasma pool of 5HT (mean change -33%) 2 hr. after administration, while platelet 5HT is unchanged. These data support the existence of a human plasma 5HT pool, with a rapid turnover, different from the 5HT in platelets (slow turnover, reserve pool). Both may be useful in evaluating different aspects of 5HT-mediated pathologies.