Circulating levels of 1-O-hexadecyl-2-acetyl-sn-glycero-3-phosphocholine (C16PAF) in human subjects were measured by gas chromatography/mass spectrometry using negative ion chemical ionization. The mean (+/- S.D.) circulating C16PAF levels in patients with essential hypertension (18.1 +/- 5.3 pg/mL, n = 16) were not significantly different from those in normotensive subjects (17.2 +/- 7.2 pg/mL, n = 14). During a salt balance study, high salt intake (20 g/day) significantly increased the circulating level of C16PAF, and changes in circulating C16PAF significantly and positively correlated with changes in mean arterial blood pressure (r = 0.47, p less than 0.05). Changes in C16PAF also correlated with changes in creatinine clearance (r = 0.55, p less than 0.05), but did not correlate with changes in plasma sodium concentration, plasma chloride concentration and plasma volume. An intravenous injection of 50 micrograms of human atrial natriuretic peptide (hANP) decreased circulating C16PAF levels from 20.0 +/- 2.7 to 13.9 +/- 2.4 pg/mL of blood (n = 10, p less than 0.01) in healthy subjects. The data appear to indicate that C16PAF levels are changed by salt intake-induced mild increase in blood pressure, and that hANP may be an endogenous factor which lowers circulating C16PAF.