OBJECTIVE To evaluate the possible biological aspects of 'unexplained physical symptoms', this study examined serotonergic and noradrenergic monoamino acids in somatoform disorders and/or depression. METHODS Blood samples of 150 subjects from 4 groups (somatization syndrome; depression; depression and somatization; controls) were analyzed for amino acids contributing to the serotonergic and noradrenergic system and peripheral muscle energy balance (tryptophan, valine, leucine, isoleucine, phenylalanine and tyrosine). RESULTS Tryptophan, branched chain amino acids and other serotonergic amino acids were decreased in patients with somatoform symptoms, even when no depression was present. CONCLUSIONS We conclude that serotonergic amino acids are biological correlates of multiple unexplained symptoms. Ways of action do not only involve brain mechanisms, but also energy metabolism in peripheral muscles.