Objective - To assess whether, on the basis of one blood test, penicillin allergy might be excluded sufficiently for general practitioners to give oral penicillin to patients claiming a history of penicillin allergy. Design - Prospective study of patients referred by general practioners. Setting - Outpatient allergy clinic in a district general hospital. Patients - 175 referred patients who gave a history of immediate type reaction to penicillin, of whom 144 attended as requested and 132 completed the investigations. Main outcome measures - History and examination, serum radioallergosorbent test to phenoxymethyl-penicillin and benzylpenicillin, and oral challenge with penicillin. Results - Of 132 patients, four were confirmed to have penicillin allergy by the radioallergosorbent test and 128 had an oral penicillin challenge without ill effect. Conclusions - Most patients who gave a history of penicillin allergy are not so allergic, and their actual allergic state should be substantiated whenever feasible. For patients reporting minor or vague reactions negative findings with a radioallergosorbent test to phenoxymethylpenicillin and benzylpenicillin provide sufficient evidence to give oral penicillin safely.