The aim of this study was to ascertain whether fibromyalgia patients with positive ANA develop other features of connective tissue disease over 2-4 years' follow-up. Patients attending our clinic with a diagnosis of fibromyalgia were identified. All ANA-positive patients (n = 12) were recruited and matched for age and sex with 12 ANA-negative FMS patients. As further control groups, patients with a diagnosis of osteoarthritis (OA) were included. A screening questionnaire for possible features of connective tissue disease was sent to all participants. Patients who had three or more positive criteria were invited for further assessment. The ANA-positive rate was 12/137 (8.8%) in FMS and 20/225 (8.9%) in OA patients. All ANA positivity was at a low titre. Fourteen out of 20 (70%) FMS patients and 17/30 (56.7%) OA patients had three or more criteria (P = 0.34). No significant differences in the number of the positive criteria were found between those who were ANA positive or negative in both groups. On full assessment we found one patient who fulfilled the criteria for SLE from the ANA-positive FMS group and one in the ANA-negative group who fulfilled the criteria for primary Sjögren's syndrome. Of the patients with OA, one who was ANA positive was diagnosed as having rheumatoid arthritis. The results from our study show that ANA (at least in low titre) is not a good predictor of the future development of connective tissue.