Patients with documented allergies to penicillin may require desensitization for treatment of severe infections, and maintenance of desensitization by continuous oral administration of the drug has been proposed. We report the case of an 11-yr-old boy with cystic fibrosis who was allergic to ticarcillin and responded to desensitization and to subsequent maintenance with oral penicillin. After an intravenous dose of ticarcillin for pseudomonas pneumonia, he devloped throat burning, periorbital edema, and pruritus, which responded to antihistamines and epinephrine. Penicillin skin testing was positive with intradermal injections of benzylpenicilloyl polylysine (36 mm 2 wheal) and 1:10,000 dilutions of 3.3 mg/ml stock solutions of minor determinant mixture (25 mm 2 wheal) and ticarcillin (25 mm 2 wheal). Intravenous desensitization to ticarcillin was performed according to a schedule similar to that for penicillin, beginning with 1:1,000,000 dilution of the proposed therapeutic dose of ticarcillin and advancing by 10-fold increments. Nasal pruritus, periorbital edema, and urticaria developed with 1:10 and full-strength dilutions but responded to antihistamine. The patient tolerated a full therapeutic-course, with occasional symptoms. To prevent need for further desensitization, the patient was begun on continuous oral penicillin (250 mg) every 12 hr. Repeat skin tests 6 wk later were negative but converted to positive (25 mm 2 wheal with undiluted ticarcillin) when the penicillin dose was decreased to 250 mg every 24 hr and prompted repeat desensitization for an infection occurring at this time. A change in oral penicillin therapy to every 8 hr ablated skin-test reactivity and allowed the use of ticarcillin without prior desensitization, with only mild nasal itching and congestion. Increasing the serum concentration of ticarcillin with the use of the renal tubular blocking agent, probenecid, produced a transient return of allergic symptoms, suggesting that the patient was only partially desensitized. This case demonstrates the successful application of penicillin desensitization procedures to a semisynthetic penicillin and maintenance of desensitization by continuous oral therapy with the parent drug.