Certain antibiotics, particularly piperacillin, have been reported to be associated with a high incidence of allergic reactions in patients with cystic fibrosis. We initiated a study to determine the relative frequency of allergic reactions, ie, drug-induced fever and rash, to parenteral beta-lactam antibiotics in adult patients with cystic fibrosis. Charts of 111 patients were reviewed for each hospitalization to assess allergic reactions. Of 90 evaluable patients, 26 patients developed one or more allergic reactions to beta-lactam antibiotics. The number of allergic reactions per number of patients receiving specific antibiotics were carbenicillin (4/56), mezlocillin (7/42), piperacillin (11/31), ticarcillin (1/20), cefazolin (0/24), ceftazidime (1/35), imipenem/cilastatin (4/16), and nafcillin (3/36). The mean time to onset of drug-induced fever or of rash was 9.1 days. As a group penicillins had a higher frequency of allergic reactions than cephalosporins. The frequency of reactions was greatest with acylaminopenicillins (mezlocillin and piperacillin) and imipenem/cilastatin. The results of this study indicate that in addition to piperacillin, mezlocillin and imipenem/cilastatin may be associated with a high incidence of allergic reactions in patients with CF.