The authors review theoretical and clinical data supporting the hypothesis that L-tryptophan may potentiate the effects of lithium carbonate and report on a double-blind clinical comparison of lithium plus L-tryptophan and lithium plus placebo in 9 bipolar and 7 schizoaffective patients. Overall the combination of lithium and L-tryptophan resulted in significantly greater improvement. However, the results may have been confounded by the greater, although nonsignificant, doses of neuroleptics administered to the group receiving L-tryptophan. The authors discuss the interactions of lithium and L-trypotophan with the serotonin system.