Investigated the role of pterins in depressive illness and examined the effect of placebo, antidepressant, and electroconvulsive therapy (ECT) on the neopterin:biopterin (N:B) ratio. 48 patients (mean age 53.9 yrs) meeting Diagnostic and Statistical Manual of Mental Disorders-III (DSM-III) criteria for major depressive disorder were studied. Ss were involved in trials of rolipram and fluparoxan; a separate group of Ss was involved in ECT treatment. Urinary excretion of neopterins and biopterins was measured in Ss before and after treatment and in 26 healthy controls. Patients prior to and after treatment had a significantly greater N:B ratio than controls. There was a significant correlation between N:B ratios and severity of depression and plasma cortisol. N:B ratio was significantly lower for all groups following treatment; improvement was greatest for the ECT Ss. Findings suggest that tetrahydrobiopterin may exert rate-limiting control over synthesis of monoamines implicated in pathogenesis of depressive illnesses.