Both jejunal nodular lymphoid hyperplasia (NLH) and polyethylene glycol (PEG)-3350 hypersensitivity are extremely rare. We describe a 30-year-old female who had previously taken a PEG-3350 bowel preparation without adverse effects, and presented for evaluation of chronic diarrhea. An upper and lower gastrointestinal endoscopy, and small bowel series were scheduled. PEG-3350 and electrolytes for oral solution was prescribed for bowel cleansing. During consumption of the bowel preparation she developed urticarial hypersensitivity. An alternative bowel preparation was used. Colonoscopy and upper endoscopy were normal, but small bowel series revealed innumerable sand-like lucencies in the jejunum. NLH was confirmed on biopsy from antegrade enteroscopy. This is the first case report on the pathological jejunal NLH in association with the PEG-3350 urticarial hypersensitivity. The potential pathophysiological etiology of this association is discussed.