The role of the sympathetic nervous system (SNS) in postnatal functional maturation of Müller's smooth muscle was evaluated in urethane-anesthetized Sprague-Dawley rats. Guanethidine treatment beginning at birth induced complete sympathectomy, as determined by abolition of contractile responses to electrical stimulation of preganglionic axons and tyramine. Through 45 days of age, sympathectomy had little effect on development of contractile responses to stimulation of alpha-1 adrenoceptors by methoxamine. In contrast, sympathectomy prevented the 2-fold increase in contractile response which normally occurs between 45 and 70 days. Similarly, treated preparations were supersensitive to methoxamine (decreased ED50) only after 45 days. Neonatal decentralization of sympathetic neurons also prevented the increase in methoxamine response occurring after 45 days. Treatment of mature rats with guanethidine from 70 to 100 days of age resulted in a 40% reduction in force of contraction. It is concluded that: the SNS is not obligatory for Müller's muscle functional maturation through 45 days; the SNS mediates a 2-fold increase in contractile response between 45 and 70 days; the effect of the SNS is impulse-dependent; and the intact SNS is required to maintain end organ function at mature levels.