The authors present the first case report of a 50-year-old woman with a 33-year history of severe, chronic watery diarrhea and hypokalemia secondary to chronic active microscopic enterocolitis with patterns similar to lymphocytic colitis but with acute cryptitis and terminal ileum involvement microscopically. The progressive nature of her illness resulted in multiple hospital admissions secondary to hypokalemia with subsequent chronic renal failure. High continuous doses of oral potassium supplements failed to correct the hypokalemic episodes. After subtotal colon resection, the patient made a marked clinical improvement with normal serum potassium levels without receiving potassium supplementation.