An account is given of the problems associated with the study of allergic reactions to drugs, illustrated by reference to penicillins and cephalosporins. The clinical relevance of some of the immunological methods which have been used is assessed. An investigation of a variety of potential penicillin and cephalosporin antigens by skin prick tests in patients with a history suggesting allergy to penicillin and in control subjects is described. There was an association between skin reactivity to penicillin and cephalosporium mycelial extracts and to A. fumigatus but not to penicillins, cephalosporins or PPL. Possible methods of studying reactions to cephalosporins by penicillin-allergic patients are discussed and the tolerance of cephalexin, cephaloridine and cephalothin by such patients is presented from analysis of the international literature