Analyses were performed to evaluate the roles of the β1‐ and β2‐adrenergic receptors in the skeletal muscle hypertrophy and anti‐atrophy response to the β‐adrenergic agonist, clenbuterol. Treatment of wild‐type mice with clenbuterol resulted in statistically significant hypertrophy of the innervated tibialis anterior and medial gastrocnemius muscles and inhibition of denervation‐induced atrophy of these muscles. Treatment of β1‐adenergic receptor knockout mice with clenbuterol also resulted in statistically significant hypertrophy of the innervated tibialis anterior and medial gastrocnemius muscles and inhibition of denervation‐induced atrophy of these muscles. In contrast, in β2‐adrenergic receptor knockout mice and in mice lacking both the β1‐ and β2‐adrenergic receptors, clenbuterol treatment did not result in hypertrophy of the innervated tibialis anterior and medial gastrocnemius muscles, nor did it inhibit denervation‐induced atrophy in these muscles. Together these data demonstrate that the β2‐adrenergic receptor is responsible for both the skeletal muscle hypertrophy and anti‐atrophy effects of the β‐adrenergic agonist clenbuterol. © 2002 Wiley Periodicals, Inc. Muscle Nerve 25: 000–000, 2002