Using a kinetic model of D-xylose absorption, we have previously shown that there is severely impaired absorption of D-xylose in HIV patients with diarrhea and weight loss. The absorptive defect is characterized by an increased rate constant for nonabsorptive loss of D-xylose, Ko, and a decreased absorptive rate constant, Ka, and is unrelated to histology or the presence of pathogens. It is not known if there is also abnormal paracellular transport in these patients. We have extended our observations in these patients by including a measurement of paracellular transport, lactulose absorption. Nine HIV patients with chronic diarrhea, weight loss, and no detectable intestinal pathogens, two healthy volunteers, and three non-HIV patients with chronic diarrhea (two functional and one with scleroderma) were enrolled. Of the nine HIV patients, six had diminished bioavailability of D-xylose, F (range: 19-52%, normal >70%), and elevated rate constant for nonabsorptive loss, Ko (range: 0.54-1.35/hr, normal <0.353/min). Four of the six also had decreased Ka (range: 0.09-0.36/hr, normal >0.634/min). Only one of these six had increased lactulose recovery (3.51%, normal <0.5%). Two of three patients with normal kinetic parameters of D-xylose absorption had increased lactulose urinary recovery (1.92%, 2.61%). In conclusion, lactulose absorption is increased in some patients with HIV-related diarrhea who have normal D-xylose absorption, suggesting a paracellular mechanism for diarrhea in some patients with AIDS enteropathy.