There is good evidence that retention products accumulating in chronic renal insufficiency influence prostaglandin (PG) synthesis, thus affecting platelet-vascular wall interaction. The vascular PGI2 synthesis is increased and prolonged in vitro, the plasma factor activity enhanced. A defective platelet function is frequently observed; it is completely restored by peritoneal dialysis, but only partially by hemodialysis. The sensitivity of platelets to PGI2 and its plasmatic degradation are unchanged. There is evidence of a shift of arachidonic acid metabolism from cyclooxygenase to lipoxygenase. These changes may be attributed to undialyzable plasma constituents, the ‘middle molecules