OBJECTIVE: To report two cases of anaphylactic reactions to proton-pump inhibitors (PPIs). CASE SUMMARIES: A 54-year-old woman who had taken omeprazole in the past was treated with omeprazole 40 mg and developed periorbital edema, edema of the skin, pruritus, nausea, and vomiting about 45 minutes after taking one capsule. Five months later, she was treated with lansoprazole 30-mg capsules. Again, within 45 minutes she developed an even more serious reaction, with pruritus and urticaria on her whole body, increased sweating, facial edema, and loss of consciousness. A 61-year-old man took one tablet of pantoprazole 40 mg one year after first being treated with the drug. Within hours after ingestion, he developed malaise, generalized pruritus and urticaria, a swollen tongue and eyes, and diffuse sweating; his blood pressure decreased to 75/50 mm Hg. DISCUSSION: Because of the acute onset of symptoms and close temporal association with exposure to the drug, as well as previous exposure to it, the reactions can be classified as anaphylactic shock to PPIs. These benzimidazole derivatives are chemically related; observations in a few patients, such as the first case above, suggest that cross-sensitivity may occur. The Uppsala Monitoring Centre (UMC) has received a total of 42 reports of anaphylactic reactions or anaphylactic shock in association with PPIs. These reports account for 0.2% of the total of reported suspected adverse drug reactions to PPIs, compared with 0.8% anaphylactic reactions in the UMC database as a whole. CONCLUSIONS: These findings suggest that the chemically related PPIs can, as a group, cause anaphylactic reactions; however, the rate is comparatively low. Since anaphylaxis is a potentially serious reaction, more precise information is needed regarding its frequency, and healthcare professionals need to be aware of this possibility when prescribing these agents.