Previous work from our laboratory has demonstrated the presence of endogenous strychnine in the mammalian brain and human serum samples. The present study examines the role of strychnine in neuropsychiatric disorders. Strychnine is synthesized from tryptophan. The blood levels of tyrosine, tryptophan, and strychnine were studied as also RBC membrane Na(+)-K+ ATPase activity. It was found that serum tyrosine levels were reduced and that tryptophan levels were elevated in all neuropsychiatric disorders studied with a reduction in RBC Na(+)-K+ ATPase activity. Strychnine was present in significant amounts in the serum of patients with epilepsy, Parkinson's disease, and manic depressive psychosis. The presence of strychnine in significant amounts could be related to elevated tryptophan levels, suggesting the synthesis of these alkaloids from tryptophan. Na(+)-K+ ATPase inhibition present in most of the disorders could be related to increased depolarizing strychninergic transmission. The role of strychnine in the pathogenesis of these disorders, in the setting of membrane Na(+)-K+ ATPase inhibition, is discussed.