A 69-year-old woman with Pseudomonas aeruginosa sepsis developed wheezing during the course of an oral penicillin desensitization. Despite treatment of the bronchospasm and readministration of the same dose of phenoxymethyl penicillin, wheezing recurred requiring stopping the desensitization procedure. Aztreonam, a monobactam antibiotic with activity against aerobic gram-negative bacilli, was administered along with an aminoglycoside. The patient tolerated a full course of aztreonam with no adverse reactions. This case report supports previous in vitro and in vivo studies, suggesting that aztreonam does not cross-react with penicillin-specific antibodies and that it may be well tolerated in beta-lactam-allergic individuals.