Failure to reveal pneumoperitoneum is a recognized weakness of abdominal sonography. Our objective is to describe a reliable and reproducible sign of pneumoperitoneum that was first identified in an animal model and then confirmed in patients who had undergone laparoscopy. We injected 300 ml of degassed water into the peritoneal cavity of a 15-kg anesthetized pig. Sonographic images were obtained of the anterior peritoneal area after intraperitoneal injection of a single bubble, a series of bubbles, and, subsequently, a 10-ml bolus of air. Later, abdominal sonography was performed in nine patients who had undergone laparoscopy. Close attention was paid to the anterior peritoneal area and signs of free air observed in the animal model. Ten healthy volunteers functioned as a control group. In the pig, minute amounts of intraperitoneal air showed on sonography as enhancement of the peritoneal stripe. Larger volumes of intraperitoneal air showed as enhancement of the peritoneal stripe associated with dirty shadowing or distal multiple reflection artifacts. The stripe enhanced each time it appeared in the reflection artifact. Intraluminal gas was associated with a normal thin peritoneal stripe, superficial and distinct from the underlying gas artifact. The patients who had undergone laparoscopy showed findings suggestive of small and large pockets of free air, as we saw in the pig model. The control group showed findings consistent with intraluminal gas only. On sonography, enhancement of the peritoneal stripe alone or with reflection artifacts involving the peritoneal stripe is an accurate sign of pneumoperitoneum.