Heparin free hemodialysis was compared to systemic heparinization, intermittent saline flushes and constant saline infusions in eight, stable chronic patients dialyzing on hollow-fiber artificial kidneys (HFAK) at blood flows of 250 to 300 ml/min. No significant differences in small molecule clearance, fluid removal or dialyzer clotting were noted. Since this data showed that heparin free hemodialysis without supplemental saline was feasible in a group of stable, chronic dialysis patients, we then prospectively studied twenty-nine patients judged to be at increased risk of hemorrhage from heparinization during 100 heparin-free dialyses. The incidences of severe and moderate dialyzer clotting were 7% and 20%, respectively. Seventeen of 27 treatments in which moderate or severe clotting occurred had identifiable factors thought to predispose to dialyzer clotting such as low blood flows, poor vascular-access function, severe hypotension and intradialytic blood transfusions. Although higher hematocrit values were associated with greater degrees of dialyser clotting, stepwise discriminant analysis employing blood flow, blood pressure, hematocrit and transfusion administration could not develop an accurate predictor or combination of predictors of clotting. No patient experienced de novo or increased bleeding and problems with inadequate dialysis were not observed. Since this method of heparin free dialysis is as safe and effective as previously reported strategies and requires no specialized equipment or procedures, it is a reasonable initial strategy for dialyzing high risk patients.