Recent studies have shown that plasma beta endorphin levels of patients on methadone maintenance are comparable to controls. Furthermore, CSF levels of related peptides in methadone patients also do not differ from controls, although CSF levels of beta endorphin have not been specifically measured. In the current study we compared both CSF and plasma levels of beta endorphin in 11 patients on methadone maintenance for at least 10 months to levels in 13 controls getting spinal anesthesia for surgery. The CSF beta endorphin levels of the methadone maintained patients were significantly higher than the controls (52.3 vs 21.7 pg/ml), while plasma levels of beta endorphin (29.6 vs 31.1 pg/ml) and cortisol (13.8 vs 12.6 micro g/dl) [corrected] did not differ. Covarying for age differences between the samples, slightly increased the magnitude of this difference in CSF beta endorphin levels. Plasma levels of beta endorphin did not correlate with CSF levels, but did correlate with plasma levels of cortisol (r = 0.51, P less than 0.02). These findings supported previous studies of plasma beta endorphin levels. However, the dissociation of beta endorphin levels in plasma and CSF within this patient population was a new finding.