To explore the hypothesis that endogenous 1-methyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline (salsolinol) might be involved in the etiology of alcoholism, its concentration was determined in the striatum and adrenal gland of rats bred selectively for disparate alcohol drinking. The alcohol-naive alcohol-preferring (P) and the high-alcohol-drinking (HAD) lines of rats demonstrated significantly lower striatal and adrenal salsolinol content when compared with the alcohol-non-preferring (NP) and the low-alcohol-drinking (LAD) lines. In the P-line of rats, 4 weeks of free-choice alcohol drinking had no significant effect on striatal salsolinol levels, although adrenal levels of salsolinol were significantly higher. The salsolinol assayed in the striatum of all lines of rats occurred as a racemic mixture of enantiomers that was unchanged following 4 weeks of alcohol exposure. Unlike striatal tissue, the adrenals of alcohol naive P-rats contained significantly more S- than R-salsolinol (ratio S/R = 83/17) and alcohol consumption resulted in the formation of a nearly racemic mixture of enantiomers. These results suggest a role for genetic factors in the formation of endogenous salsolinol and its potential regulation by short-term alcohol intake.