A pharmacokinetic model for minimal dose heparinization for chornic hemodialysis patients was recently described by Gotch and Keen. The model requires the determination of two parameters: dose sensitivity (computed for a given heparin dose from increase in WBPTT above a baseline value) and the heparin elimination constant. This study describes the extension of this model to the more precise control of anticoagulation during routine dialysis. S and K were measured in 30 stable chronic dialysis patients and were found to differ markedly (0.015 less than or equal to S 0.08 sec/unit; 0.04 less than or equal to K less than or equal to 1.7 hr-1). The mean S value was 0.041 +/- 0.002 sec/unit (N = 30) and the mean K value was 0.90 +/- 0.06 hr-1 (N = 30). In addition, the mean t 1/2 of heparin obtained in the group of 30 patients from individual rate constants was 0.86 +/- 0.06 hr, in excellent agreement with values obtained in normal subjects given similar doses of the drug. Variations in sensitivity during dialysis were minimal, but variations in elimination rate of up to 50% were encountered during modeling. However, the large variations in K did not affect the applicability of the model of control clotting times during dialysis when infusion requirements were based on mean values of S and K taken over four to five dialyses. In an initial group of five patients, whose heparin requirements were reduced by an average of 38% +/- 20 (range 13% to 65%), there was no significant change in the degree of dialyzer clotting in comparing premodeling and postmodeling heparin therapy. In most of the remaining patients (N = 22) the pattern was similar: a reduction in total heparin administration without increased dialyzer clotting. In three patients (10%) over-all heparin dose had to be moderately increased (3% to 13%). Heparin modeling has been successfully applied to routine anticoahe technique cannot be extended to other clinical procedures involving either intermittent or continuous infusion of heparin. To assist in the application of heparin modeling, nomograms have been developed.