In summary: 1) Are the principles of the orthomolecular hypothesis reasonable and testable? They are reasonable and they would be more testable if more specific. 2) Is there evidence that there are deficits consistent with this theory in some schizophrenics? The recent findings of a deficit in methylenetetrahydrofolate reductase in an adolescent diagnosed as schizophrenic and treated with folic acid (2), the finding of a possible genetically determined deficiency in platelet monoamine oxidase in some schizophrenics (24), and the finding that some chronic patients respond to a massive dose of the serotonin precusor 5-hydroxytrytophan compared with placebo (25) are consistent with these views. 3) Is there scientific justification for the claims made by megavitamin therapists? Certainly the more extravagant ones, including those made and quoted by Pauling, are not supported by the evidence. 4) Does the weight of scientific evidence indicate that megavitamin therapy as currently used is beneficial? No. In fact, there are no double-blind studies showing megavitamins to be useful in the way they are currently used.While the concepts of orthomolecular psychiatry are attractive and stimulating, the data supporting them are weak, and therapeutic claims based upon them are unwarranted.Abstract Teaser