The aetiologic evaluation of adverse cutaneous reactions to penicillins is still not an easy problem to solve. Skin testing is usually carried out intradermally with benzylpenicilloyl polylysine (BPO-PPL) and minor determinant mixture (MDM), but these are often unsuitable for the detection of sensitivity to betalactam antibiotics. 101 selected subjects, with different cutaneous reactions to betalactams and with a clinical history of positive challenge, were skin tested (patch test, prick test, intradermal test) with a standard betalactam series (amoxycillin, sodium penicillin G, ampicillin, bacampicillin, aztreonam, ceftriazone, BPO-PPL, MDM). 1 or more positive reactions to skin tests, mainly to intradermal tests, were observed in 47.5% of the subjects studied, especially in those with maculopapular eruptions, urticaria/angioedema and drug reactions caused by ampicillin and amoxycillin. Cross-sensitivity was demonstrated in 22.8% of cases and was due almost solely to the semisynthetic penicillins. Finally, to increase the yield in detecting positive patients, it is necessary that ampicillin and amoxycillin be tested in addition to major and minor determinants.