Plasma and platelet levels of 5-hydroxytryptamine (5 HT) may be altered in essential hypertension. To establish the determinants and correlates of 5 HT in plasma and platelets, we studied 53 untreated subjects with essential hypertension (26 men; 30 whites; mean supine blood pressure 172/101 mm Hg; mean age 49.3 ± 1.5 years) and 61 normotensive subjects (37 men; 47 whites; mean supine blood pressure 128/78 mm Hg; mean age 42.8 ± 1.6 years). Plasma and platelet 5 HT were assayed by reverse-phase high performance liquid chromatography with electrochemical detection. No significant difference was found in platelet-poor plasma or platelet 5 HT levels in hypertensive or normotensive subjects (plasma: 43.0 ± 4.2 and 39.6 ± 4.4 nmol/L; platelet: 1.65 ± 1.22 and 1.70 ± 1.39 nmol/10⁹ cells in hypertensive and normotensive subjects, respectively). No significant correlation was found between plasma or platelet 5 HT and systolic or diastolic blood pressure (plasma: r = 0.01 and 0.01 in normotensive subjects and r = 0.01 and –0.14 in hypertensive subjects; platelet: r = 0.12 and 0.13 in normotensive subjects and r = 0.02 and –0.09 in hypertensive subjects). However, plasma 5 HT was associated with supine and standing pulse rates (supine: r = 0.27, p = 0.05 in normotensive subjects and r = 0.54, p < 0.001 in hypertensive subjects; standing: r = 0.19 and r = 0.46, p < 0.001, respectively). Significant relations were also found between platelet 5 HT levels and supine and standing heart rate in the subjects mentioned above (supine: r = 0.28, p = 0.05 in normotensive subjects and r = 0.64, p < 0.001 in hypertensive subjects; standing: r = 0.24 and r = 0.51, p < 0.001, respectively). These associations were stronger in the hypertensive group as a whole, and they held when adjustment was made for differences in age and total blood cholesterol. The present study showed that plasma and platelet 5 HT are not significantly altered in hypertensive subjects. However, plasma and platelet 5 HT levels showed a significant association with supine and standing pulse rate predominantly in hypertensive subjects. This is consistent with experimental evidence of a positive chronotropic effect of 5 HT on perfused hearts and it suggests a possible role of plasma serotonin in the regulation of heart rate. (Am Heart J 1998;135:838-43.)