Epinephrine content and PNMT activity in medulla pons and hypothalamus of F344 inbred rats is from 3- to 8-fold higher than that of Buf inbred rats. These strain-dependent differences in brain adrenergic neurons are reciprocally related to altered alpha 1- adn alpha 2-adrenergic receptor density in PNMT-containing brain regions. Radioligand binding indices related to alpha 2-receptor function reveal that receptors may be 'desensitized' as well as 'down-regulated' in the strain with high PNMT activity (F344), and may be 'supersensitive' as well as 'up-regulated' in the strain with low PNMT activity (Buf). The association between epinephrine-containing neurons and alpha-adrenergic receptor regulation appears specific, since alpha-adrenergic receptor density and regulation in brain regions devoid of PNMT and epinephrine is similar in F344 and Buf rats. While noradrenergic metabolism in F344 rats is greater than that in Buf rats, this difference is generalized throughout the brain and, thus, bears no apparent relationship to the localized alterations in alpha-adrenergic receptor density. Moreover, beta-adrenergic receptor density in the 2 strains is similar in all brain regions. These data suggest that a significant proportion of alpha-adrenergic receptors in medulla-pons and hypothalamus are intimately related to and regulated by epinephrine-containing nerve endings.