Cerebrospinal fluid (CSF) levels of beta-endorphin (beta-EP) were measured in 9 migraineurs with interparoxysmal headache (MIH), in 13 patients with major depression in an active phase (5 suffered from MIH), and in 16 age-matched controls. beta-EP was measured by specific RIA after gel-chromatography. While beta-EP levels of depressed patients (58.5 +/- 21.0 fmol/ml, M +/- SD) were similar to those of controls (65.8 +/- 26.6), those of migraineurs (15.0 +/- 11.1) were significantly reduced (p less than 0.01). In depressed patients also suffering from MIH, beta-EP concentrations (22.8 +/- 7.2, p less than 0.05) were half those reported in depressed patients without pain problems. The reduced CSF beta-EP levels in patients whose headache and depression coexist support the notion that this neuropeptide is concerned with chronic pain, independently of the affective state.