Fibromyalgia is a musculoskeletal disorder characterized by generalized myalgias, arthralgias widespread tender points in discreet areas on examination. It is frequently accompanied by fatigue, stiffness, and a nonrestorative sleep pattern. These patients generally have a normal blood count and chemistry profile. There is a subset of people with fibromyalgia (FM) who test positive for the antinuclear antibody (ANA) and have constitutional symptoms that resemble those of patients with early lupus. We studied the immunologic profile of patients with FM who are ANA-positive (+). A retrospective review of patient records in a university-based rheumatology practice was conducted. In a group of 66 FM patients, 30% (20) were ANA+, with a 75% preponderance of the speckled pattern and 20% diffuse pattern. The remaining 5% were equally split between diffuse-speckled and speckled-nucleolar patterns. All had negative staining for extractable nuclear antibodies. The Smart Index (SI), a ratio of the sedimentation rate to one-half the patient's age, was developed to characterize each patient's inflammatory response. The FM patients who were ANA negative (-) had a mean SI of 0.55, whereas the FM patient's who were ANA+ had a SI of 1.07. These ANA+ patients represent a subgroup of patients who have FM with an inflammatory response profile larger than that of the ANA-patients.