We have examined the effects of six tryptolines (tetrahydro-beta-carbolines) upon 5-hydroxytryptamine (5-HT) uptake into rat forebrain homogenates. All six were found to be competitive inhibitors of 5-HT uptake. 5-Hydroxytryptoline, the most potent inhibitor, had an inhibitor constant (Ki) of 0.3 mugM. Both 5-hydroxytryptoline and 5-hydroxymethtryptoline were also shown to be relatively selective against 5-HT uptake, being 20 times less potent against norepinephrine uptake and 40 times less potent against dopamine. Since it is possible that tryptolines might be formed as a result of alcohol consumption, these results suggest that it is important to examine the possibilities that such compounds mediate some of the effects of alcohol upon serotonergic pathways.