The effect of intraoperative blood loss on serum levels of cefazolin in patients being managed with total hip arthroplasty was studied. Eighteen patients, thirteen men and five women, with a mean age of sixty-five years (range, forty to eighty-five years) were enrolled in the study. Fifteen had a primary total hip arthroplasty and three, a revision.Each patient served as his or her own control. Baseline clearance of cefazolin was determined at a minimum of forty-eight hours before the operation. Each patient received one gram of cefazolin intravenously. Serial serum concentrations were determined from specimens drawn at zero, five, ten, twenty, thirty, sixty, 120, 240, and 300 minutes after administration. Fifteen minutes before the skin incision was made, each patient again received one gram of cefazolin intravenously. Serum samples were collected at the same time-intervals, and the serum levels of cefazolin were determined with use of capillary electrophoresis. Data regarding intraoperative blood loss as well as replacement of fluid and blood were recorded. The administration of the antibiotic, retrieval of the serum samples, and estimation of the blood loss were performed by the same person in the same manner for all patients.The preoperative and intraoperative creatinine clearances (mean and standard deviation), estimated with use of the formula of Cockcroft and Gault, were 62.06 ± 21.28 and 74.02 ± 24.75 milliliters per minute, respectively. The amount of intraoperative blood loss averaged 1137 ± 436 milliliters (range, 675 to 2437 milliliters). The preoperative and intraoperative cefazolin clearances averaged 0.49 ± 0.21 and 0.52 ± 0.30 milliliter per minute per kilogram, respectively.During joint replacement, the commonly accepted interval between doses of cefazolin is four hours. In the present study, the serum level of cefazolin at four hours was forty-five micrograms per milliliter. This corresponds to an osseous concentration that well exceeds the minimum inhibitory concentration for Staphylococcus aureus, which is 0.5 microgram per milliliter. This study suggests that, with blood losses of less than 2000 milliliters, it is not necessary to administer cefazolin at intraoperative intervals of less than four hours in order to maintain a concentration of antibiotics that is higher than the minimum inhibitory concentration for the most common infecting organisms.