This study was conducted to evaluate the effects of an SH-radical in an angiotensin converting enzyme (ACE) inhibitor on PGI2 generation, intracellular cGMP, and Ca2+ kinetics in vascular endothelial cells. In the cultured human umbilical vein endothelial cells, the non-SH containing ACE inhibitors, delapril and enalapril, did not result in significant changes in cGMP concentrations. By comparison, captopril significantly (P less than .01) increased cGMP concentrations. Only captopril showed a significant (P less than .01) effect on 45Ca kinetics in cultured human vascular endothelial cells. Captopril also decreased PGI2 generation in vascular endothelial cells. These effects were not seen with delapril or enalapril. The significance of the SH moiety in ACE inhibitors remains controversial. However, these results suggest that there could be differences in the vascular actions of ACE inhibitors related to the presence or absence of SH radical.