Platelet function was studied in 34 patients during 74 hemodialyses by means of a Cordis-Dow hollow fiber hemodialyzer (CDAK-4) with anticoagulation by porcine mucosal heparin. The mean arterial platelet levels fell 11% from predialysis values and remained stable throughout a 5 hr hemodialysis session. After 30 min of dialysis, the platelet concentration in afferent and efferent limbs of the dialyzer were similar, although retention of leukocytes was apparent. As measured by platelet aggregometry, heparin was clearly shown to potentiate the extent of aggregation induced by low concentrations of ADP. Platelets of the dialyzer afferent limb were less aggregable than normal and resistant to aggregation induced by submaximal concentrations of ADP or epinephrine. Platelets of the dialyzer efferent limb were aggregable only after excessive stimuli of 50 micrometer ADP or 10 micrometer epinephrine. These findings suggest that direct contact between dialyzer fibers and platelets or rheological effects led to impaired platelet function but that most platelets are not irreversibly injured.