A variety of retroperitoneal diseases such as pancreatitis, infection, and trauma may cause fluid collections in the three major retroperitoneal spaces. The purpose of our study was to elucidate flow patterns of fluid between the various compartments to assist the clinical-radiologic assessment and treatment of various retroperitoneal diseases. In eight cadavers, CT guidance was used to selectively inject 35-1000 ml of contrast medium by hand or power injector into five perirenal, two posterior pararenal, and two anterior pararenal spaces. After the injections, CT of the entire abdomen and pelvis was done with 10-mm-thick sections at intervals of 10-40 mm. All images were reviewed in detail by a group of experienced body imagers to assess the pathways of flow of contrast material between the three major retroperitoneal spaces. The caudal cone of perirenal fascia was uniformly patent. A narrow channel connected the two perirenal spaces in the midline; the posterior border of this channel abutted the anterior margins of the abdominal aorta and the inferior vena cava. The perirenal, anterior pararenal, and posterior pararenal spaces all communicated with the infrarenal space, which in turn connected with the extraperitoneal spaces in the pelvis. When large quantities of contrast medium are injected in the perirenal or pararenal spaces and the infrarenal space is filled, the infrarenal space may then serve as a conduit across the midline of the abdomen. The anterior pararenal space crossed the midline and had a distinct retrorenal extension but no intraperitoneal connection. The slender posterior pararenal space had an anterolateral extension en route to the prevesical space. Our findings show pathways and extensions of the perirenal, anterior pararenal, and posterior pararenal spaces that should be considered when assessing a variety of retroperitoneal diseases. Perinephric collections, such as hematomas and urinomas, have at least a potential conduit across the midline or into the pelvis. Our study explains how blood from a ruptured abdominal aortic aneurysm may enter either perinephric space. Anterior pararenal processes, such as pancreatitis or appendicitis, can extend into the pelvis or cross the midline, and posterior pararenal blood from trauma can also flow into the pelvis.