The penetration of cefetamet and cefuroxime into the maxillary sinus mucosa after the administration of cefetamet pivoxil and cefuroxime axetil was investigated in patients undergoing elective surgery of the maxillary sinus. A total of 27 patients, 13 for cefetamet pivoxil and 14 for cefuroxime axetil, ranging from 15 to 70 years of age participated in this study. Each patient received three oral doses of either one tablet of cefetamet pivoxil (500 mg of GLOBOCEF) or two film tablets of cefuroxime axetil (125 and 250 mg of ZINAT) every 12 h. Sinus mucosa tissue samples were removed during surgery at times ranging from 2 to 4.5 h after the last oral administration. Blood samples were collected before drug administration, 2 h after the first and third doses, and concomitantly with tissue sample collection during surgery. All samples were analyzed by high-performance liquid chromatography. The concentrations of cefetamet and cefuroxime in plasma samples measured concomitantly with those in tissue samples ranged between 0.83 and 4.5 micrograms/ml for cefetamet and 0.59 and 3 micrograms/ml for cefuroxime. The mean tissue-to-plasma ratios calculated with reference to total (bound plus unbound) plasma drug concentrations were 0.60 (range, 0.52 to 0.77) for cefetamet (n = 4) and 0.38 (range, 0.28 to 0.44) for cefuroxime (n = 6). Both drugs seem to penetrate freely and easily into the sinus mucosa. The antibacterial activities of cefetamet pivoxil and cefuroxime axetil in cases of sinusitis therefore depend mainly on their achieved active plasma drug concentrations and their intrinsic activities in inhibiting the causative organism(s).