Fibromyalgia is a chronic, painful musculoskeletal disorder characterized by widespread pain, pressure hyperalgesia, morning stiffness and by an increased incidence of depressive symptoms. The etiology, however, has remained elusive. The aim of the present study was to examine the inflammatory response system (IRS) in fibromyalgia. Serum interleukin-6 (IL-6), soluble IL-6 receptor (sIL-6R), sgp130, sIL-1R antagonist (IL-1RA) and sCD8 were determined in 33 healthy volunteers and in 21 fibromyalgia patients, classified according to the American College of Rheumatology criteria. Severity of illness was measured with several pain scales, dolorimetry and the Hamilton Depression Rating Scale (HDRS). Serum sgp130 was significantly higher and serum sCD8 significantly lower in fibromyalgia patients than in healthy volunteers. Serum sIL-6R and sIL-1RA were significantly higher in fibromyalgia patients with an increased HDRS score (> or = 16) than in normal volunteers and fibromyalgia patients with a HDRS score < 16. In fibromyalgia patients, an important part of the variance in sCD8 (50.3%) and IL-1RA (19.3%) could be explained by the HDRS score; 74.3% of the variance in sIL-6R was explained by the combined effects of pain symptoms and the HDRS score; and 25.9% of the variance in serum sgp130 was explained by stiffness. The results support the contention that pain and stiffness in fibromyalgia may be accompanied by a suppression of some aspects of the IRS and that the presence of clinically significant depressive symptoms in fibromyalgia is associated with some signs of IRS activation.