Forty patients undergoing hysterectomy and 16 patients undergoing colorectal surgery were given intravenous 2 g doses of cefotetan (20 in the hysterectomy group and 8 in the colorectal group) or cefoxitin (20 in the hysterectomy and 8 in the colorectal group) before surgery. Serum samples were obtained simultaneously with tissue samples. Concentrations of each drug in serum and tissue were measured by high-pressure liquid chromatography. In both experiments, the composite drug concentration profile as a function of time in serum was consistent with that observed in nonsurgical patients; that is, a half-life of approximately 3.5 hours and 0.8 hours for cefotetan and cefoxitin, respectively. This also was true of tissue kinetics, in that tissue profiles appeared parallel to, but somewhat lower than, serum. At 20 minutes after administration, the peak myometrium concentration was 158 micrograms/g for cefotetan, and the corresponding serum concentration was 298 micrograms/ml. For cefoxitin, the corresponding values were 66 micrograms/g and 101 micrograms/ml. At 47 minutes, the cefotetan tissue and serum concentrations were 29 micrograms/g and 235 micrograms/ml respectively, and the corresponding values for cefoxitin were 15 micrograms/g and 43 micrograms/ml. Similar relationships were observed with these drugs in colorectal tissue. Although both antibiotics provide good concentrations during the early phase of surgery, cefotetan's concentrations persisted longer, which may be relevant in the prevention of infection in prolonged surgical procedures.