Sodium polystyrene sulfonate (Kayexalate) in sorbitol given as an enema or orally to treat hyperkalemia has been reported to induce intestinal necrosis in uremic patients. We studied the clinical and pathologic features of 15 patients in whom Kayexalate crystals were observed in specimens from gastrointestinal surgical resections (n = 9) or endoscopic biopsies (n = 7). Oral or nasogastric tube administration of Kayexalate in sorbitol was documented in 10 patients. Among 12 patients with colorectal specimens, necrosis was observed in nine patients (75%), represented by seven of eight surgical resection specimens and three of five endoscopic biopsy specimens. No other cause of colorectal necrosis apart from Kayexalate in sorbitol was apparent in seven patients, and four also had necrosis of the small intestine. Four patients with colonic necrosis in their initial resection specimen developed progressive necrosis of the small intestine or rectum, and five patients (56%) had fatal outcome within 1 day to 6 weeks. Kayexalate crystals were observed in upper gastrointestinal tract specimens from four patients, including one with hemorrhagic gastritis. Our findings provide additional evidence that Kayexalate in sorbitol administered orally or by nasogastric tube can produce necrosis in the gastrointestinal tract.