The influence of aging on the molecular forms of endorphins in the hypothalamus of rats was investigated. Extracts of individual hypothalami from 8- and 24-month-old male Fischer 344 rats were subjected to high-performance liquid chromatography. Eluate fractions were assayed for β-endorphin-like immunoreactivity (βE-LI) and γ-endorphin-like immunoreactivity (γE-LI). Hypothalami from adult (8-month-old) rats contained predominantly β-endorphin-1–31 with smaller amounts of β-endorphin-1–27 and 1–26. Only 5% of the βE-LI co-eluted with α-N-acetylated forms of β-en-dorphin. In hypothalamic extracts from old rats more than 30% of the βE-LI co-eluted with acetylated forms of β-endor-phin and over 35% of the βE-LI co-eluted with acetylated or unacetylated β-endorphin-1–26. The individual elution profiles of βE-LI were also much more variable among the old rats than among the adult rats. More than 80% of the γE-LI from adult rat extracts co-eluted with γ-endorphin (β-endorphin-1–17) and less than 3% with α-N-acetyl-γ-endorphin. In contrast, more than 35% of the γE-LI from old rat hypothalami was present in the acetylated form. These results suggest that significant alterations in post-translational processing of peptides may occur in neur