Risk factors for the development of carpal tunnel syndrome in women were studied by means of a nested case-control analysis of a prospective cohort study of the health effects of oral contraception in British women. A total of 1,264 women who had a diagnosis of carpal tunnel syndrome reported by their general practitioner between 1968 and 1993 were compared with 1,264 age-matched control women who did not have this diagnosis. The syndrome was associated in older women with some hormonal factors, notably past use of oral contraception (adjusted odds ratio in women aged 40 years and over = 1.38, 95 percent confidence interval: 1.08, 1.76) and more generally with obesity (adjusted odds ratio = 1.68, 95 percent confidence interval: 1.29, 2.18). However, the strongest link was with a previous history of another musculoskeletal complaint for which consultation had been sought (adjusted odds ratio = 1.98, 95 percent confidence interval: 1.61, 2.42). Previous findings of a higher risk in women with diabetes and myxoedema were confirmed, but these contribute only a small proportion of all cases in women. There was no link with psychologic problems or nonmusculoskeletal pain complaints. The previously described increased incidence of carpal tunnel syndrome in women may be partly due to hormonal factors, but is also related to an underlying propensity to musculoskeletal problems and their higher overall frequency in women.