A synergistic antiplatelet effect between prostaglandin I2 (PGI2), a cAMP-stimulator, and nitric oxide (NO), a cGMP-stimulator, has been described. Data on a PGE1-NO interaction, however, are lacking so far. We therefore examined the question in healthy volunteers, whether a similar synergism exists between PGE1 and NO on human platelets in vitro. Each of the substances alone caused a dose-dependent inhibition of ADP-induced platelet aggregation, PGE1 (1ng/mlPRP) reduced platelet aggregation by 27.8 +/- 14.6%, NO (0, 3%) by 26, 7 +/- 25, 5%. The combination of these compounds caused an additive effect resulting in a reduction of 40, 6 +/- 23, 5%. The findings indicate that PGE1 (like PGI2) and NO have a synergistic antiplatelet action. The concomitant treatment with both compounds offers an interesting concept for clinical therapy.