Three new broad-spectrum penicillins--azlocillin, mezlocillin, and piperacillin--will soon be available for clinical use. Azlocillin and piperacillin are more active than carbenicillin or ticarcillin against Pseudomonas aeruginosa. Piperacillin and mezlocillin demonstrate significant activity against the Enterobacteriaceae, including many strains of Klebsiella pneumoniae against which the older penicillins carbenicillin, ticarcillin, and ampicillin are ineffective. All three new drugs show substantial activity against anaerobes and ampicillin-susceptible gonococci and Haemophilus influenzae. Because these agents are inactivated by various beta-lactamases, most Staphylococcus aureus isolates and a number of gram-negative organisms, including some important nosocomial pathogens, will be resistant to these antibiotics. The new penicillins appear to be relatively safe and have been used successfully to treat patients with various infections; however, comparative trials have not yet established the superiority of these drugs over conventional therapeutic agents.