Eleven biological markers (plasma amino acids, cortisol, prolactin, oestrogen, progesterone, thyroxine, thyrotropin, folate, vitamin B-sub-1-sub-2, urinary biopterins, and neopterins) were measured in 33 male and 30 female patients with Diagnostic and Statistical Manual of Mental Disorders-III-Revised (DSM-III-R) major depression. The results were compared with those obtained in 32 male and 38 female normal controls. Male depressive Ss had significantly lower plasma levels of tryptophan, cysteine, thorine, ornithine, tryptophan/large neutral amino acids (LNAA) ratio, folate, vitamin B-sub-1-sub-2, oestrogen, and thyroid-stimulating hormone levels than normal controls. Male depressive Ss, however, had significantly higher plasma levels of methionine and thyroxine than control Ss. Depressed females had fewer significant differences with lower plasma levels of histidine, ornithine, glutamine, and tryptophan/LNAA ratio, and higher plasma levels of arginine, and higher plasma levels of arginine, cortisol, and prolactin than female controls. The results are consistent with those obtained in Western populations and support the notion of a universal biologic substrate for depression