The proximal tubule (PT) reabsorbs the majority of sodium, bicarbonate, chloride ions, phosphate, glucose, water, and plasma proteins from the glomerular filtrate. Despite the critical importance of endocytosis for PT cell function, the organization of the endocytic pathway in these cells remains poorly understood. We have used immunofluorescence and live-cell imaging to dissect the itinerary of apically internalized fluid and membrane cargo in polarized primary cultures of PT cells isolated from mouse kidney cortex. Cells from the S1 segment could be distinguished from more distal PT segments by their robust uptake of albumin and comparatively low expression of -glutamyltranspeptidase. Rab11a in these cells is localized to variously sized spherical compartments that resemble the apical vacuoles observed by electron microscopy analysis of PT cells in vivo. These Rab11a-positive structures are highly dynamic and receive both membrane and fluid phase cargo. Moreover, we observed segregation of membrane proteins and fluid phase cargoes into separate carriers emanating from Rab11a-positive compartments. In contrast, fluid phase cargoes are largely excluded from Rab11a-positive compartments in immortalized kidney cell lines. The unusual morphology and sorting capacity of Rab11a compartments in primary PT cells may reflect a unique specialization of these cells to accommodate the functional demands of handling a high endocytic load.