Moxalactam, a novel beta-lactam antimicrobial agent in which oxygen has replaced sulfur in the six-membered ring of the conventional cephem nucleus, has in vitro activity against almost all commonly isolated bacterial pathogens including Staphylococcus aureus, the Enterobacteriaceae, Pseudomonas aeruginosa, Bacteroides fragilis, and Haemophilus influenzae. The clinical efficacy an toxicity of moxalactam alone was evaluated in the treatment of 100 infections, including 22 septicemias. Thirty-two infections involved P aeruginosa, while organisms resistant to one or more of the currently available cephalosporins or cefoxitin were isolated from cultures in 63 of the cases. The overall clinical response was favorable (infection cured or improved) in 86% of the infections. A child with Klebsiella pneumoniae ventriculitis and meningitis was cured with intravenous moxalactam alone. Six of 14 treatment failures involved P. aeruginosa, and P aeruginosa isolates resistant to moxalactam emerged during therapy of 12 infections. Side effects, usually mild diarrhea, occurred in only 8.8% of the patients. Except for some severe P aeruginosa infections outside the urinary tract, moxalactam is effective and safe single-agent therapy for infections caused by susceptible organisms and represents a major advancement in beta-lactam antimicrobial therapy.