Penicillin allergy presents a major obstacle to the successful management of some antepartum infections. We studied 15 pregnant women with histories of penicillin allergy confirmed by positive immediate wheal-and-flare skin tests. Thirteen had syphilis, one listeria sepsis, and one Streptococcus viridans endocarditis. Each patient was desensitized over four to six hours by oral administration of increasing doses of penicillin V. At the completion of the procedure, full-dose parenteral therapy with penicillin G or ampicillin was instituted. No extracutaneous reactions were detected. Five of the subjects (33 per cent) experienced pruritus (three) or urticaria (two), but no interruption of desensitization or therapy was necessary. All clinically apparent maternal infections were cured. The pregnancy complicated by listeriosis aborted in the first trimester. The 11 neonates delivered to date are normal. These results indicate that oral desensitization is an acceptably safe approach to therapy in pregnant women who are allergic to penicillin and have infections that require beta-lactam drugs.