The disposition of heparin was studied in 21 chronic hemodialysis patients. Heparin was administered as a bolus injection in doses of 3,000-12,000 U. Combined zero and first-order elimination was demonstrated, with heparin half-life declining by 74% over 3.5 h during dialysis. Assumption of a first-order pharmacokinetic model of elimination resulted in a mean difference of 0.001 U/ml between actual and predicted heparin concentrations. Mean first-order pharmacokinetic parameters were: half-life, 117 min; heparin volume of distribution (V), 68 ml/kg; clearance, 28 ml/min. A high degree of interpatient variability was also observed. A comparison of V and plasma volume (PV) revealed V to be significantly greater than PV (p less than 0.001), indicating distribution outside the plasma compartment. When compared to blood volume, there was no significant difference (p greater than 0.1), indicating that blood volume may be used to approximate V. The nonlinear component of the elimination process is not clinically significant within the range of therapeutic plasma concentrations used during hemodialysis, but the high degree of interpatient variability indicates that dosage individualization may be useful.