Heparin was measured, with respect to standard curves prepared with normal pooled plasma, by five methods, APTT, (Auto-APTT), thrombin time (Thromboquik), one (Heptest) and two-stage (Hepaclot) coagulation, anti-factor Xa and chromogenic anti-factor Xa after addition at three concentrations (0.2, 0.4, 0.6iu/ml) to plasma prepared from three groups of ten individuals: normal young volunteers, hospitalized patients with malignancy and hospitalized geriatric patients. By the APTT and TT, differences in sensitivity were observed, for example, at 0.4iu heparin/ml corresponding to an apparent difference in heparin level of 10- and 14-fold between high and low responding individuals. All low responders, by APTT and TT, were in the older hospitalized group, tending to overheparinization when monitoring by these methods. Such large differences were not apparent by any of the anti-factor Xa assays. A circadian difference (1.9 and 1.8 fold) in sensitivity was also observed in the patient group such that in samples taken at night (12 pm), heparin levels were 30-50% higher than those taken during the morning on average when measured in the APTT and TT (p,0.001, analysis of variance). Again, such large differences were notapparent by anti-factor Xa methods. In light of recent findings about the usefulness of anti-factor Xa methods for efficient monitoring of heparin, it issuggested that this conclusion may arise from the tendency for anti-factor Xa methods to determine actual concentrations of heparin.