Allergic reactions to beta-lactams are the most frequent adverse reactions to drugs, but conventional methods of detection of beta-lactam specific IgE detect only a low number of positivities. In this study we evaluated the diagnostic reliability of one of these methods (CAP FEIA, Pharmacia) which has been proven very useful in inhalant and food specific IgE determinations. We studied specific IgE to penicillin G, penicillin V, amoxicillin and ampicillin in 1078 patients who had been diagnosed with an adverse reaction to beta-lactams, and out of this group, in a selected subgroup of 149 patients with a very suggestive clinical history of beta-lactam anaphylactic reaction. Also, positivity of specific IgE was studied in a group of 58 patients with a clinical history of immediate hypersensitivity to beta-lactams and with positive skin tests, and positivity of skin tests was studied in a subgroup of 13 patients with positive specific IgE. To increase the sensitivity of IgE determinations, we concentrated 5-fold the sera from six selected patients. In the first group we found that penicillin G specific IgE was positive in 28% of the cases when considering a cutoff > or = class 1, and 6% when considering a cutoff > or = class 2. For penicillin V, positivities were 9% (> or = class 1) and 4% (> or = class 2). In the second group, we found 31.81% sensitivity and 88.57% relative specificity of CAP FEIA with respect to the skin test. In the group of 58 patients with a clinical history of immediate hypersensitivity to beta-lactams, we found a disagreement between skin testing and specific IgE determination in 28.2%, and a positive agreement in 9.4% of the cases. After sera concentration, there was a significant increase (p < 0.001), from 0.58 to 1.61 kU/l, in beta-lactam specific IgE. Our results suggest that skin testing offers greater reliability and sensitivity than beta-lactam specific IgE determination by CAP FEIA.