The duration of effective anticoagulation with heparin during cardiac catheterization and angiography was determined in 201 patients. Effective anticoagulation was defined as prolongation of the activated partial thromboplastin time (APTT) by 2 or more times the upper limit of normal. When the procedure was completed within 40 min of heparin administration, all patients were anticoagulated adequately. The incidence of inadequate anticoagulation ranged from 9% to 25% as the time from heparin administration increased to 89 min. Procedures completed more than 90 min after heparin administration had a 58% incidence of inadequate anticoagulation. A protocol to estimate the appropriate protamine dose was developed based on experience accumulated in the first 78 patients and tested subsequently in 101 consecutive patients. Clotting studies returned to the normal range in 92% of the patients. The mean APTT decreased from 84.1 +/- 19.4 to 27.4 +/- 2.5 sec (p less than .001) after protamine. Patients who did not correct to normal after protamine remained only 2.8 +/- 1.4 sec (range 0.7-5.5 sec) above normal. These data provide an estimate of the duration of anticoagulation during cardiac catheterization and angiography and demonstrate the feasibility of a simple and reliable method to reverse the effects of heparin.