We measured serotonin (5HT) levels in platlet-poor plasma (PPP) from premature newborns. 5HT is a neurotransmitter and a powerful vasopressor with specific vascular receptor sites as well as α-adrenergic receptor activity. 5HT is actively taken up and metabolized by the pulmonary vascular endothelium. This specific pulmonary 5HT uptake has been demonstrated in adult humans as well as in fetal and newborn animals. Animal models suggest that the 5HT uptake ability of the lung is greatest in the newborn period. 5HT is present in neuroendocrine cells (NEC) which are most numerous in the lung during the perinatal period, and animal studies suggest that 5HT may be released from NEC in response to alveolar hypoxia. Imbalances in circulating 5HT levels have been associated with changes in vascular hemodynamics. 46 samples (0.2 cc PPP) were obtained from 29 premature newborns (27-36 wks gestation). Samples were taken on days 2-3 and 6-7 of life. 17 of these represent paired serial samples. 5HT levels were measured using a precolumn sample enhancement technique followed by ion exchange HPLC with electrochemical detection. The average 5HT on days 2-3 was 1.67 ± 0.65 ng/ml [mean ± 95% con. limit], and on days 6-7 was 0.74 ± 0.26 ng/ml (P=.03). Moreover, in 16 of 17 paired samples 5HT fell over time (P<.025). 5HT levels did not appear different with respect to gest. age or the need for supplemental O2. We conclude that: 1) PPP 5HT values in premature newborns are low, 2) there is a significant decline in these values over the first week of life, and 3) in contrast with adults and animal models, the presence respiratory distress is not associated with increased PPP 5HT levels.