In insulin-dependent diabetics (IDDM) and peripheral occlusive arterial disease (POAD), inhibition of platelet aggregation (PA) by PGI2and PGE1was reduced (p<0.02) compared with non-diabetics and POAD as well as with healthy subjects at a similar extent of PA (in the 3 groups). c-AMP content in resting platelets of IDDM and chronic renal failure was decreased (mean±SD in pmo1/2.5×108platelets): 5.3±1.1 compared with the content in healthy subjects: 8.0±1.12 andP<0.012. Moreover, c-AMP content in PGE1-stimulated platelets was also reduced in these patients. Our results indicate that diabetic patients are characteristically less sensitive to inhibition by the 2 prostanoids, presumably through attenuated activity of the c-AMP generating system.