The effects of chronic dynamic exercise on myocardialβ-adreneegic and muscarlnlc cholinergic receptors and chronotropic sensitivity to isoproterenol were studied in 5 Yucatan mlniswine. Right atrial and left ventricular biopsies, heart rate responses to isoproterenol, and maximal exercise treadmill testing were obtained before and after 10–19 weeks of treadmill running. Radioligand studies using125I-iodocyanopindolol (ICYP) and3H-quinuclidinyl benzilate (QNB) were used to determine the number ofβ-adrenergic and muscarinic cholinergic receptors. Maximal oxygen consumption increased from 52 ± 5 to 65 ± 7 ml/kg/min (mean ± SD;p<0.02), maximal workload from 530 ± 111 to 1,074 ± 179 KPM/min (p<0.01), resting heart rate decreased from 91 ± 13 to 62 ± 4 beats/min (p<0.01), heart rate at 75% of pretraining maximal workload decreased from 253 ± 15 to 196 ± 12 beats/min (p<0.01), and maximal exercise heart rate decreased from 273 ± 6 to 254 ± 9 beats/min (p<0.01). Decreased heart rate responsiveness to adrenergic stimulation was observed following chronic exercise. Maximal isoproterenol-stimulated heart rate decreased from 225 ± 13 to 185 ± 28 beats/min (p< 0.05) and the slope of the isoproterenol dose-response relation decreased from 63 ± 16 to 40 ± 16 (p<0.05). Radioligand studies revealed a decrease inβ-receptor number in the right atrium following chronic exercise (61 ± 9 vs. 34 ± 8 fmol/mg;p<0.02), but receptor number in membranes from the left ventricle did not change (60 ± 9 vs. 62 ± 4 fmol/mg). There was no change in muscarinic cholinergic receptor number in right atrial membranes following the training period (204 ± 73 vs. 230 ± 92 fmol/mg). Thus, chronic dynamic exercise results in down-regulation ofβ- adrenergic receptors in the right atrium and is associated with reduced chronotropic responsiveness to exercise and isoproterenol stimulation.