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The effect of maximal exercise on lymphocyte beta-adrenergic receptors was examined in 26 normal subjects. Exercise increased O2 consumption (Vo2) from 5 +/- 1 to 50 +/- 4 ml.min-1.kg-1, plasma norepinephrine level from 188 +/- 28 to 2,682 +/- 160 pg/ml, and plasma epinephrine level from 94 +/- 72 to 857 +/- 180 pg/ml. The density of beta-adrenergic receptors on lymphocytes obtained at rest was 31 +/- 3.7 fmol/mg protein; exercise increased the density of receptors by 86 +/- 33% (range 0–257%) to 58.3 +/- 1.5 fmol/mg protein but did not alter the affinity of the receptor for [125I]iodopindolol or the coupling of the receptor to the guanine nucleotide-binding regulatory protein. The density of beta-adrenergic receptors increased progressively throughout exercise and paralleled the increase in heart rate. The magnitude of the change in the density of beta-adrenergic receptors did not correlate with the magnitude of the increase in heart rate, Vo2, or plasma levels of catecholamines. The density of receptors was still elevated 15 min after completion of exercise but fell below base line 1 h after peak exercise to 18.2 +/- 6.7 fmol/mg protein (P less than 0.05 vs. base-line levels). These results demonstrate that exhaustive exercise results in a progressive increase in the number of beta-adrenergic receptors on lymphocyte membranes, followed by a reduction in the density of receptors during the recovery phase of exercise. Despite a significant increase in the level of plasma catecholamines, the receptor remains coupled to the guanine nucleotide-binding regulatory protein.