In this double-blind study, beta-endorphin, 4-15 mg, was administered intravenously to 6 schizophrenic and 4 depressed patients. There were neither significant differences in behavioral ratings between beta-endorphin and placebo for the overall group nor for either the schizophrenic or depressed subgroup. Clinical worsening and improvement were observed in individual schizophrenic patients. There was no evidence of late-appearing therapeutic effects in 4 schizophrenic patients rated for 5 consecutive days after placebo and drug infusions. In 1 patient 10 mg of beta-endorphin produced neuroendocrine effects comparable to those produced by 5 mg of intravenously administered methadone; in 2 other patients it produced large increases in circulating opioid activity as determined by radioreceptor assay. These biological data support the notion that parenterally administered beta-endorphin exerts significant opiate-like activity in vivo.