Subacute treatment with toluene (80-1500 p.p.m.) produces a dose-dependent reduction of affinity and increase in density of the beta-adrenergic antagonist [3H]dihydroalprenolol binding sites in the frontoparietal cortex of the male rat, while the binding characteristics of alpha 1-adrenergic ([3H]WB 4101) and alpha 2-adrenergic ([3H]p-aminoclonidine) binding sites in the same region is unaffected by this treatment as evaluated in vitro. Therefore, it is suggested that the cortical beta-adrenergic receptors are particularly vulnerable to the action of toluene in vivo. It is speculated that as a result cortical beta-adrenergic neurotransmission may be altered following exposure to low concentrations of toluene, possibly related to the physico-chemical properties of toluene, leading to changes in membrane fluidity.