More than 50% of AIDS patients suffer from diarrhea, the cause of which is unexplained in 15-40%. In 60-85% a potential cause for diarrhea could be found but the pathogenic relevance often remains unclear. In this paper we review the current knowledge about the nonmalabsorptive mechanisms for diarrhea in HIV infection from a pathophysiologic point of view and we show evidence that the diarrhea in advanced HIV infection by HIV per se could be caused by a leak flux mechanism due to an epithelial barrier defect.