When solutes and water are transported across epithelial tissues such as the intestine, they may take one of two pathways: through cells and/or between cells. To this date transport through cells has been studied in enormous detail. Our good understanding of transcellular transport and its regulation has helped us appreciate the mechanisms of animal adaptation to fresh- and saltwater, it has led to the discovery of the molecular defect in cystic fibrosis, and it has aided the development of new drugs (diuretics). The mechanisms of transport between cells are just now beginning to receive attention. A major advance in this direction was made during the previous NSF award period in the laboratory of the PI: the first demonstration that an extracellular peptide (leucoknin, a neurohormone) regulates a transport pathway outside the cell. Whether this pathway is between cells, the so-called paracellular pathway, is the first and most important objective of the continuation of this work. The second objective is the detailed examination of the ion pump located in the cell membrane facing the urine side of the kidney. The third objective is to discover new hormones involved in the regulation of transport. This work is done in isolated kidneys of insects, the so-called Malpighian tubules of the yellow fever mosquito.