To evaluate the safe use of aztreonam (AZT) in patients allergic to penicillins and other beta-lactam antibiotics we studied 29 patients from a group of subjects allergic to beta-lactams, diagnosed by presenting systemic reactions after skin tests or challenge tests. Skin tests with benzylpenicilloyl (BPO), benzylpenicilloate, benzylpenicillin, ampicillin, amoxicillin, cephamandole and AZT, radioallergosorbent test (RAST) to BPO and AZT, RAST inhibition and challenge tests were performed. One patient was skin test-positive to AZT, another patient was RAST AZT-positive. IgE antibodies were specific to AZT as demonstrated by RAST inhibition studies with AZT coupled to epsilon-amino caproic acid. Nevertheless, AZT was unable to inhibit either a pool of sera or individual sera positive to BPO. Although all our 29 patients tolerated the administration of AZT (including those with skin test or RAST positive) and AZT appears to be safe in these subjects, this does not indicate that all beta-lactam-allergic patients tolerate AZT administration.