Sera from 204 patients with acute or former reactions following penicillin treatment were investigated by RAST with specificity for benzylpenicilloyl and phenoxymethyl-penicilloyl. The IgE antibody levels were followed up for of more than 2 years. Positive results could be observed at the time of the acute reactions and the weeks following; later months or years in many cases. Occasionally negative RAST results occurred within 30 days; on the other hand high levels of specific IgE persisted for years in some patients. Total serum IgE measured by RIST and the RAST results showed similar patterns, with mean levels of 568 u/ml between 0 and 30 days after the penicillin allergic reaction, 286 u/ml between 30 days and 1 year, and 195 u/ml in cases after 1 year corresponded well with the observed decline in specific IgE. Skin tests performed with penicilloyl-polylysine in 118 patients showed an overall correlation of 91-5% with the RAST results. Differences between the two test systems were observed in patients with a long interval between the test and the last allergic attack. None of the patients with proved penicillin allergy had atopic diseases or a history of atopy. On the basis of these findings it is suggested that the determination of both circulating specific IgE and total IgE should be of great value for diagnostic purposes during acute drug reactions and in the months immediately afterwards.