Cyclic GMP, endothelin and prostaglandin E2 (PGE2) all have systemic vasoactive properties (with cyclic GMP acting as a second messenger of nitric oxide). Intrarenally they act as natriuretics and urinary levels reflect intrarenal production. Cyclic GMP and PGE2 also act as important inhibitors of platelet activation and thrombosis. The purpose of this study was to determine if urinary levels of cyclic GMP, endothelin, and PGE2 differ in preeclamptic as compared to normal pregnancies. Parameters were compared in 13 normotensive, nonpreeclamptic pregnancies, and 32 preeclamptic pregnancies. Preeclamptic women had significantly lower levels of urinary cyclic GMP (0.67 +/- 0.12 vs. 2.1 +/- 0.5 nmol/g creatinine), endothelin (0.88 +/- 0.09 vs. 3.75 +/- 1.4 ng/g creatinine), and PGE2 (26 +/- 4 vs. 9 ng/g creatinine) as compared to normals (p < 0.05). Intrarenal production of cyclic GMP, endothelin, and PGE2 are all disturbed in preeclampsia and may have implications in the sodium retention, hypertension, and intrarenal thrombosis and vasospasm of preeclamptic pregnancy.