The activity of RU29246, the active metabolite of the oral cephalosporin ester HR916, was compared in a multicenter study with that of the four oral beta-lactam antibiotics cephalexin, cefaclor, cefixime and amoxicillin/clavulanate (amoxicillin/CA). RU29246 was generally 2- to 8-fold more active than the other oral cephalosporins and comparable to amoxicillin/CA against staphylococci, and was the most active cephalosporin against group B streptococci. All four cephalosporins were ineffective against enterococci. RU29246 was the only cephalosporin consistently active against Acinetobacter, but all beta-lactam antibiotics had poor activity against Pseudomonas spp. and Xanthomonas maltophilia. RU29246 was comparable to cefixime and more active than the other cephalosporins against members of the family Enterobacteriaceae. However, all of the antibiotics had poor activity against Enterobacter cloacae and Serratia marcescens. Quality control reference ranges for the quality control organisms Staphylococcus aureus ATCC 29213 and Escherichia coli ATCC 25922 are proposed for the broth dilution method based on data derived from this multicenter study.