Microvillus inclusion disease is an inherited intestinal brush border membrane defect that causes severe fluid and electrolyte malabsorption. In an infant with microvillus inclusion disease (confirmed by electron microscopic evaluation of rectal, jejunal, and gallbladder mucosae), basal stool output was massive (> 125 mL · kg −1 · day −1) and was not altered by treatment with clonidine or octreotide. A proximal jejunostomy with mucous fistula was placed, allowing separation of proximal from distal tract outputs (60 mL · kg −1 · day −1 and 100 mL · kg −1 · day −1, respectively). A 10-cm jejunal segment was excised during surgery and mounted in Ussing chambers for determination of transepithelial Na + and Cl − fluxes. Compared with intestine of normal infants, this infant's epithelium showed transmural conductance and unidirectional ion fluxes that were only 30% of normal. With respect to both Na + and Cl −, the excised jejunum was in a net secretory state. Theophylline (5 mmol/L) increased net Cl − secretion slightly. In response to mucosal d-glucose (30 mmol/L), jejunal mucosal-to-serosal Na + flux doubled. In the infant, glucose-electrolyte solution administered intrajejunally did not significantly change stool output, suggesting that all of the solution (40 mL/kg) was absorbed. Subtotal enterocolectomy, in theory, could have decreased purging by 66% in this infant with microvillus inclusion disease, but diarrhea would still have been significant.