The exchanges of ¹²⁵I-labeled 4-iodoantipyrine (I-Ap), ¹⁴C-labeled antìpyrine (¹⁴C-Ap), and tritiated water (THO) were studied in isolated blood-perfused, beating, nonworking dog hearts. From a first set of experiments, analysis of externally monitored myocardial clearance curves of I-Ap after its injection into coronary artery blood showed its washout to be flow limited at flows ranging from 0.8 to 3.8 ml · g⁻¹ · min⁻¹. Therefore, these curves can be used for estimating coronary blood flow. In a second set of experiments, coronary sinus dilution curves of simultaneously injected I-Ap and THO were found to be indistinguishable in shape at high coronary flows. At low flows (<1.8 ml · g⁻¹ · min⁻¹), THO curves showed an earlier upslope and higher peak than antipyrine, indicating either a diffusional shunt for water or a larger volume of distribution for antipyrine. ¹⁴C-Ap had a slightly faster washout than I-Ap. The differences are partially attributable either to differences in solubility of I-Ap, ¹⁴C-Ap, and THO in erythrocytes or to differences in their volumes of distribution, and partially to diffusional shunting of water.