Aims: Allergy to recombinant human (rDNA) insulin preparations is a rare complication of insulin therapy. However, insulin preparations contain several allergens, and several disorders can resemble insulin allergy. Studies evaluating the diagnostic procedures on suspected insulin allergy are extremely few. Methods: Since January 1998, we have used a standardized investigative procedure during admittance to the medical ward allowing observation and repeated recording of reactions to intradermal skin test (performed with a commercially available kit containing isolated insulin allergens). Data on all investigated cases until April 2003 were collected retrospectively, and self-reported efficacy of intervention was compared to clinical data. Results: Twenty-two patients were included. In nine (41%) cases, non-insulin allergic causes were discovered and successfully treated: poor injection technique (n = 5), skin disease (n = 3) and other systemic allergy (n = 1). Nine other patients were found to be allergic to protamine (n = 3) or rDNA insulin (n = 6), and specific treatment was associated with relief in 8 patients (89%). Four patients had local reactions of unknown causes but symptom relief was obtained in three cases by unspecific therapy. Overall, 20 (91%) reported relief of symptoms. Conclusion: Our standardized investigative procedure of suspected insulin preparation (IP) allergy was associated with relief of symptoms in > 90% of patients. IP allergy was diagnosed in 41%, and intradermal testing with isolated insulin allergens was a prerequisite in identification of culprit allergen and targeting of treatment.