Primary systemic allergy to human insulin is rare. We report a case of recurrent immediate local reactions followed eventually by generalized urticaria to recombinant human insulin (Humulin) in an insulin-dependent diabetic. Skin test to Humulin R was positive, and the patient was successfully desensitized using a modified rapid desensitization protocol. Two weeks later, he had another episode of generalized urticaria after Humulin R injection. His treatment was resumed at a lower dose, and within a week he was able to tolerate his usual regimen of insulin. To our knowledge, this is the first report of a recurrence of systemic reaction after successful desensitization.