The purpose of this study was to ascertain if alterations were present in the prostacyclin synthetase (PGI2ase) activity in diabetic human venous tissue. Saphenous veins were obtained from a group of 12 patients with (HSV-D) or without (HSV-ND) diabetes who were undergoing coronary artery bypass surgery. 14C-Labeled prostaglandin endoperoxide (PGH2) was incubated for 2 minutes with venous microsomal protein. The products were separated by thin-layer chromatography and quantified by radiochromatographic scan. PGI2ase activity was determined by the formation of 6-keto-PGF1 alpha, the stable breakdown product of prostacyclin (PGI2). Results of this study indicate the following: both HSV-ND and HSV-D specimens have active PGI2ase and are capable of forming PGI2; there is no difference between PGI2ase activity in HSV-D and HSV-ND specimens; and in diabetes mellitus, any defects in PGI2 production similar to those associated with diabetes in other investigations must reside higher in the arachidonic acid cascade.