41 (33%) of 123 patients with acute psychiatric disorders (DSM III diagnosis of major depression or schizophrenia) had borderline or definite folate deficiency (red-cell folate below 200 micrograms/l) and took part in a double-blind, placebo-controlled trial of methylfolate, 15 mg daily, for 6 months in addition to standard psychotropic treatment. Among both depressed and schizophrenic patients methylfolate significantly improved clinical and social recovery. The differences in outcome scores between methylfolate and placebo groups became greater with time. These findings add to the evidence implicating disturbances of methylation in the nervous system in the biology of some forms of mental illness.