Previous studies have provided evidence of an increased sensitivity to pain, a decreased hypothalamic opioid tone, and decreased cerebrospinal fluid (CSF) beta-endorphin (beta-EP) concentration in patients with primary chronic headache. We applied separate specific radioimmunoassays for beta-EP in CSF and plasma on samples from age-matched controls and a group of 50 patients with chronic tension-type headache (CTH) fulfilling the diagnostic criteria set by the International Headache Society. Median CSF beta-EP concentrations (95% confidence limits) were 12.8 pmol/l (11.0-14.5) in CTH patients and 11.9 pmol/l (10.9-14.2) in the control group, which is not significantly different (P = 0.28). Plasma beta-EP concentrations did not differ either, being 3.1 pmol/l (2.4-3.7) and 3.3 pmol/l (1.8-4.0) in the patients with CTH and in controls, respectively (P = 0.88). Plasma and CSF beta-EP concentrations did not correlate. Reversed-phase high performance liquid chromatography (HPLC) of CSF pools from the headache patients and controls revealed similar profiles of beta-EP-immunoreactivity both when C-terminally and N-terminally directed antisera were used, suggesting a normal post-translational processing of the pro-opiomelanocortin gene in patients with CTH. beta-EP is not involved in the pathogenesis of CTH, or such a role is not reflected in CSF or plasma concentrations of the neuropeptide.