OBJECTIVE To establish that serological indicators of synthesis of collagens I and III in humans with normally healing tibial shaft fractures will display a temporal pattern consistent with the sequence of expression of these collagens observed histologically in animal models of fracture healing. METHODS Prospective. METHODS Four district general hospitals in the United Kingdom supported by an academic unit. METHODS Twenty consecutive patients with isolated tibial shaft fractures were studied. On clinical and radiological grounds, seventeen of the cases united within twenty weeks; these seventeen cases formed the material for this review. METHODS Nineteen patients were treated conservatively, and a functional brace was applied at five weeks. One patient treated with an external fixator had a functional brace applied at twelve weeks. METHODS Assays of collagen I carboxy-terminal propeptide (PICP), collagen III amino-terminal propeptide (PIIINP), and collagen I carboxy-terminal telopeptide (ICTP) were made in serum samples taken at standard intervals from twenty-four hours to twenty weeks after fracture. RESULTS PICP showed a significant, transient early drop, whereas ICTP rose, indicating early breakdown with uncoupling of collagen I formation and degradation. PIIINP levels rose significantly from day eight to week five, in keeping with early expression of collagen III in experimental fracture callus. PICP levels showed a gradual rise, consistent with later expression of collagen I. CONCLUSIONS The changes observed are in keeping with previous histological work on animal fracture models, suggesting that serological measures may reflect events occurring at the fracture site and thus offer a means for noninvasive and dynamic observation of collagen synthesis after fracture. Final proof that such measurements reflect bony healing per se, as opposed to events in other tissues, would require comparison with similar data from a soft tissue injury model.