SUMMARY The purpose of the present study was to compare the effects of N-dimethyl propranolol (DMP), the quaternary derivative of propranolol, and propranolol on the transmural distribution (endo/epi) of coronary blood flow in normal and ischemic regions of the myocardium. The distribution of blood flow between subendocardium and subepicardium of a nonischemic region and one distal to a severe left clircumflex coronary artery stenosis was determined by use of tracer microspheres (15,) in intact dog hearts. DMP (1, 5 and 10 mg/kg I.V.) produced a small dose-related increase in endo/epi of the nonischemic region (1.15 0.04-1.24 ± 0.05), whereas a larger increase was observed in the ischemic region (0.61 0.08-1.09 ± 0.10). DMP also produced a significant increase in ischemic subendocardial blood flow (0.59 0.12-0.76 i 0.11 ml/min/g). Similarly, propranolol (0.5 and 1.0 mg/kg I.V.) produced a small increase in endo/epi of the nonischemic region (1.18 ± 0.08-1.30 ± 0.07) and a larger increase in the ischemic region (0.72 ± 0.17-1.18 ± 0.09). However, propranolol did not increase ischemic subendocardial blood flow. It is concluded that DMP may be an alternative to propranolol in certain types of acute myocardial ischemia when 3-adrenergic blockade is undesirable.