Gastroesophageal reflux is a common condition caused mainly by motility disorders of the upper gastrointestinal tract. The most effective therapy combines acid suppression with a promotility agent. Nizatidine is a well-tolerated and effective histamine-2 (H2)-receptor antagonist used to suppress gastric acid secretion. Animal and human studies have conclusively demonstrated that nizatidine also has prokinetic activity comparable to that of cisapride, and its effect is evident <1 hour after administration of doses commonly used in clinical practice. This prokinetic activity occurs through noncompetitive inhibition of acetylcholine; this inhibition approximates the inhibition caused by neostigmine. Nizatidine appears to possess a prokinetic mechanism that may be helpful in treating patients with gastroesophageal reflux.