Sildenafil slows down the gastric emptying of a liquid test meal in awake rats and inhibits the contractility of intestinal tissue strips. We studied the acute effects of sildenafil on in vivo intestinal transit in rats. Fasted, male albino rats (180-220 g, N = 44) were treated (0.2 mL, iv) with sildenafil (4 mg/kg) or vehicle (0.01 N HCl). Ten minutes later they were fed a liquid test meal ( 99m 99m 99m 99m 99m technetium-labeled saline) injected directly into the duodenum. Twenty, 30 or 40 min after feeding, the rats were killed and transit throughout the gastrointestinal tract was evaluated by progression of the radiotracer using the geometric center method. The effect of sildenafil on mean arterial pressure (MAP) was monitored in a separate group of rats (N = 14). Data (medians within interquartile ranges) were compared by the Mann-Whitney U-test. The location of the geometric center was significantly more distal in vehicle-treated than in sildenafil-treated rats at 20, 30, and 40 min after test meal instillation (3.3 (3.0-3.6) vs 2.9 (2.7-3.1); 3.8 (3.4-4.0) vs 2.9 (2.5-3.1), and 4.3 (3.9-4.5) vs 3.4 (3.2-3.7), respectively; P < 0.05). MAP was unchanged in vehicletreated rats but decreased by 25% (P < 0.05) within 10 min after sildenafil injection. In conclusion, besides transiently decreasing MAP, sildenafil delays the intestinal transit of a liquid test meal in awake rats. Sildenafil citrate belongs to a class of compounds called phosphodiesterase (PDE) inhibitors. PDEs constitute a family of enzymes that hydrolyze cyclic nucleotides (cyclic adenosine monophosphate and cyclic guanosine monophosphate, cGMP) and play a critical role in the modulation of the second messenger pathway (1). Sildenafil citrate is a selective PDE type 5 inhibitor widely used due to its therapeutic efficacy in human erectile dysfunction and pulmonary hypertension. It effectively blocks the PDE 5-mediated hydrolysis of cGMP inside vascular smooth muscle cells, relaxing the arterioles that supply the corpus cavernosum (2) and the lung parenchyma (3).Sildenafil increases the gastric resistance to injury by non-steroidal anti-inflammatory drugs (4), decreases the distal esophageal peristalsis (5), and inhibits the gastric emptying of test meals both in humans and rats (6,7), and decreases the contractility of isolated duodenal strips (8).Since the gastrointestinal transit rate results from a complex interplay between gastric tonus, distal stomach phasic activity and resistance and propulsion offered by the small intestine (9), we measured the effect of sildenafil on the small bowel intestinal transit of a liquid test meal in awake rats.