The pharmacokinetics of the oral cephalosporins cefaclor, cephradine and cephalexin were examined following single 500 mg oral doses to fasted, healthy volunteers. Absorption of the 3 compounds was rapid following a brief lag period and peak serum levels were obtained in 1-1.5 h. Serum levels of cefaclor tended to be lower than those of cephradine and cephalexin during the 2-5 h postdosing period and cefaclor was eliminated more rapidly than other cephalosporins from serum. No difference was observed in the overall bioavailability of the 3 antibiotics based on comparable FD/V [distribution volume] values. Urine levels of the 3 cephalosporins greatly exceeded the minimum inhibitory concentrations of susceptible organisms during 0-6 h postdosing, but were considerably reduced during the 6-12 h collection period. Total urinary recovery of antibiotic activity accounted for almost 90% of dosed cephradine and cephalexin compared to 55% of dosed cefaclor. Lower serum levels and reduced urinary recovery of intact cefaclor are probably due primarily to its chemical instability. The reduced levels of cefaclor may be compensated for therapeutically by its greater in vitro antibacterial activity.