Plasma levels of tetrahydrobiopterin (BH4) and the related pterin folate were concurrently measured in 20 pairs of depressed patients and age-matched controls. The mean values of plasma BH4 in depressed patients was significantly elevated to a level about 150% of that found in the controls. Folate levels were not different between groups. These findings emphasize that BH4, a required cofactor in the biosynthesis of catecholamines and indolamines, is altered in depression.