The pharmacological and microbiological properties of cyclacillin were discussed and its usefulness in the management of a variety of infections was reviewed. The antibacterial spectrum and clinical utility of this agent generally parallels that of ampicillin, but there are minor differences in specificity with regard to individual microorganisms. The in vitro activity of cyclacillin against gram-negative pathogens varies greatly, the results fluctuating in accordance with the composition of the assay medium or method. The drug has demonstrated excellent therapeutic-effectiveness against experimental infections produced by both gram-positive and gram-negative pathogens, thus making questionable a prediction of therapeutic effectiveness from in vitro susceptibility tests alone. Cyclacillin is more resistant to β-lactamase hydrolysis than ampicillin, is much better absorbed when given by mouth and, as a result, the levels reached in the blood and in the urine are considerably higher than those obtained with the same dose of ampicillin. Cyclacillin produces fewer and milder side-effects than ampicillin.