It has been considered by some workers that sister-chromatid exchange (SCE) frequencies are elevated in patients with scleroderma and systemic lupus erythematosus (SLE). However, these observations were based on limited numbers of patients. Other have postulated the presence of a defect in DNA repair in cells from patients with various connective tissue diseases, including scleroderma and SLE. We report our findings from a large survey of SCE frequencies in patients with connective tissue diseases. Their diagnoses are scleroderma, SLE, rheumatoid arthritis, juvenile chronic arthritis, Behcet's syndrome and polyarteritis nodosa. These patients had never received cytotoxic drugs. Healthy individuals, hospital patients with diagnoses other than connective tissue disease and relatives of patients with scleroderma have been used as controls. The results have been analysed by generalized linear modelling, and we have shown that patients with SLE and Behcet's syndrome and controls with viral infections have elevated SCE frequencies, both before and after adjustments have been made for the effect on SCEs of an individual's age, smoking habits, sex and race. The SCEs of patients with scleroderma and their relatives were normal. SCE frequencies increased with age by 4% per decade and the SCE frequencies of smokers were approximately 12% higher than those of nonsmokers of similar age. The sex of an individual did not significantly affect SCEs but individuals from the Middle East were found to have lower counts than those originating from other parts of the world.