A chronic administration of isoproterenol hydrochloride (60 mg/kg body weight; 30 days) alters the collagen metabolism in denervated gastrocnemius muscle of mice. Hydroxyproline assay for collagen showed an increase in collagen content by 47%, 44%, and 61% in innervated gastrocnemius + drug, denervated control, and denervated + drug, respectively, in gastrocnemius muscles after 30 days of drug administration. Collagen proliferation is beta-agonist (isoproterenol) specific confirmed with the simultaneous administration of beta-antagonist propranolol (100 mg/kg body weight; 30 days). Van Gieson staining showed heavy collagen proliferation in the epimysium region of the muscle section and adventitia of blood vessels and some specialized regions. However, denervated gastrocnemius muscle represented a heavy collagen proliferation in the endomysium region, which also is probably responsible for extensive collagen proliferation in denervated muscle after drug administration. The SDS-PAGE of pepsin-soluble collagen revealed five bands from origin to the point of migration, gamma, beta1, beta2, alpha1, and alpha2. The SDS-PAGE of CNBr-treated pepsin-insoluble collagen pointed toward the more prominent remodeling of collagen metabolism in the beta-agonist-induced denervated gastrocnemius muscle after drug administration. From the present study, we can conclude that beta-agonist, isoproterenol hydrochloride, augments collagen proliferation in innervated as well as in denervated gastrocnemius muscle.