Previous studies have demonstrated that glial cells in culture express several subtypes of functional adrenergic receptors. To determine if similar receptors are expressed by glia in vivo, we examined the expression of adrenergic receptors in the normal, crushed, and transected optic nerves of the rabbit and rat using quantitative receptor autoradiography. Additionally, we examined the expression of adrenergic receptors in the normal and damaged human optic nerve. High levels of alpha 1-, alpha 2-, beta 1-, and beta 2-adrenergic receptors were identified in the rabbit and rat forebrain. In the normal rabbit, rat, and human optic nerves, only alpha 1 and beta 2 receptors were observed, and these were present in low to moderate densities. Combined immunohistochemistry and autoradiography suggests that the majority of beta 2-adrenergic receptors in the rabbit, rat, and human optic nerve are expressed by astrocytes. After unilateral optic nerve crush or transection, only beta 2- adrenergic receptors were significantly increased. This increase in beta 2 receptors was first detectable at days 7 and 28 post-transection in the rabbit and rat, respectively. The expression of beta 2 receptors in the transected optic nerve continued to increase with time, so that by 90 d post-transection the density of beta 2 receptors in both the rabbit and rat optic nerve was among the highest of any area in the forebrain. Taken together with previous studies, these results suggest that in vivo, beta 2-adrenergic receptors may provide a therapeutic target for regulation of astrocyte functions including glycogen metabolism, cytokine release, and the hypertrophy and proliferation that occurs in response to neuronal injury.