Acute renal impairment secondary to interstitial nephritis is a rare complication of omeprazole. We describe a 50-year-old woman who took 20 mg omeprazole twice daily for endoscopically proved ulcerative esophagitis. At the same time, Duke's C colonic cancer was diagnosed and completely resected. Five fluorouracil/folinic acid adjuvant chemotherapy was tolerated without diarrhea or mouth ulceration. Renal function was normal before her first monthly cycle but markedly deteriorated immediately before the second cycle was due. The patient was symptomatic with lethargy, nausea, and mild vomiting, but she was clinically normotensive and only mildly dehydrated. Her serum creatinine concentration increased despite prolonged intravenous hydration, peaking at 4.4 mg/dl 1 week later. Results of a renal ultrasound were normal, and urinary microscopic findings were unremarkable. Renal biopsy showed interstitial nephritis, and renal function improved on cessation of omeprazole, eventually returning to normal. We describe the 12 cases of omeprazole-induced interstitial nephritis reported previously.