The aim of the present study was to investigate whether there is a difference in evening/nocturnal interleukin-6 (IL-6) serum excretion in patients with primary insomnia compared to controls. We hypothesized that in insomniac patients, the excretion of evening/nocturnal IL-6 is enhanced, like observed in aged adults and after sleep deprivation in healthy subjects. We studied IL-6 serum concentrations in 11 patients (two males and nine females) with primary insomnia and 11 age and gender-matched healthy controls. Sleep was monitored polysomnographically for three consecutive nights. The measurement of IL-6 (from 19:00 h to 09:00 h) in 2-h intervals were performed prior to and during the last laboratory night. Polysomnographically determined sleep parameters and subjective ratings of sleep demonstrated clear-cut impairments of sleep in the insomniac group. Nocturnal IL-6 secretion was significantly increased (p<.05) in insomniac patients for the whole measurement period (mean area under the curve+/-SD: 27.94+/-14.15 pg/ml x 2h) compared to controls (16.70+/-7.64 pg/ml x 2h). Total IL-6 secretion correlated inversely with subjectively perceived sleep quality and amount of slow wave sleep in the insomniac patients. Amount of Wake Time correlated positively with IL-6 excretion in insomniacs. The results of the present study demonstrate significantly increased nocturnal IL-6 secretion in insomniacs. It might be speculated that chronic primary insomnia with polysomnographically documented sleep impairments activates the production of IL-6 analogous to sleep deprivation studies in healthy subjects. This might also implicate a higher risk for inflammatory and cardiovascular diseases in patients with chronic insomnia.