The ability of the heparin dose-activated coagulation time (ACT) response curve to predict doses of heparin during open-heart operations has been debated since its proposal. The dose-response method was examined in a statistically rigorous manner in 23 patients. The ACT response to 3 mg/kg heparin varied among patients from 308 to 520 s. Although at the start of bypass, ACTs often increased beyond the linear part of the dose-response curve (500 s), they returned to 483.7 ± 176.8 s (SD) within 1 h. After this first hour, one to four additional data points fit the initial two-point dose-response curve closely, and additional points did not significantly change dosage calculations for heparin and protamine. After a dose of protamine calculated to exactly neutralize heparin, the average ACT returned to within 7 ± 11% (SD) of control values. A two-point dose-response curve, generated for each patient before bypass begins, remains statistically valid and clinically useful throughout open-heart operations as long as the ACT is less than 500 s. The dose-response method is a simple, valid way to control coagulation during open-heart operations.