The pharmacokinetic parameters of moxalactam were compared with those of cefoperazone and cefotaxime in normal volunteers in a crossover manner. Following 30-min intravenous infusions of 2 g of each of the three antibiotics, serum levels at 1 hr were slightly lower for moxalactam (88 micrograms/ml) than for cefoperazone (112 micrograms/ml) but more than three times those obtained for cefotaxime (29 micrograms/ml). By 8 hr, levels of moxalactam (9.2 micrograms/ml) were slightly higher than those of cefoperazone (6.5 micrograms/ml), and levels of cefotaxime in serum were unmeasurable (less than 1 micrograms/ml). These values reflect differences in half lives of the three agents. Peak serum levels following intramuscular injection and serum levels during constant intravenous infusion were similar for moxalactam and cefoperazone because of counterbalancing differences in the apparent volume of distribution and rates of elimination of the two antibiotics. Serum levels of cefotaxime were much lower than those of the other two antibiotics primarily because of the rapid elimination of cefotaxime from the body. The kidney was the major route of excretion of moxalactam, whereas extrarenal mechanisms were more important for elimination of cefoperazone. These differences in pharmacokinetics may have significant implications for the clinical use of these new antibiotics.