We report the predictive value for hip fracture of a new marker of bone resorption, serum C-telopeptide of type I collagen (CTX), measured on a new automated analyzer, Elecsys. Baseline urinary and serum samples from 212 patients who subsequently had a hip fracture and from 642 controls were analyzed in a nested case control study within the EPIDOS prospective cohort. Each fracture patient was matched with three control patients of the same age who did not fracture. Mean follow-up was 3.3 years (maximum 4.9 years). We measured urinary CTX, urinary free deoxypyridinoline, and serum CTX. Urinary markers were assessed to know whether the magnitude of prediction of hip fracture by this serum marker was similar compared with that given by urinary markers. In the whole group, serum CTX was not predictive of hip fracture risk. When the analysis was restricted to samples taken in the early afternoon (between 1 and 2 P.M.), representing 115 fracture cases and 293 controls, serum CTX was significantly predictive with a relative hazard of 1.86 (95% confidence interval 1.01-3.76) for values above the premenopausal range (mean + 2 SD). For comparison, in the whole group, the relative hazard for fracture of women having a T-score >/= 2 for urinary CTX and free deoxypyridinoline was 1.67 (1.19-2.32), and 2. 07 (1.49-2.9), respectively. Serum CTX from morning samples did not predict hip fractures probably because it was not controlled for time and fasting/nonfasting state. We conclude that serum CTX sampled under controlled conditions significantly predicts the subsequent risk of hip fracture in ambulatory elderly women, with the same magnitude as urinary markers of resorption.