The mechanisms of transport of water and solutes across both hydrophilic and lipophilic pathways in the capillary wall were investigated. Paired measurements of the osmotic reflection and solute permeability coefficients of a lipid soluble solute (antipyrine MW 188 or aminopyrine 231) and a hydrophilic solute (glucose 180) were made on individually perfused capillaries of frog mesentery at temperatures between 5 and 25 degrees C. Below 15 degrees C, the lipophilic pathway accounts for less than 10% of the flux of antipyrine across the capillary wall, whereas at 25 degrees C the lipophilic pathway accounts of 50% of the flux. These results conform to the hypothesis that water and both hydrophilic and lipophilic solutes share an extracellular pathway, but water and lipids cross the cell by entirely separate routes. Both the activation energy for antipyrine and aminopyrine diffusion in the lipophilic pathway (25.9 kcal/mol) and the estimated cell membrane-water partition coefficients of the solutes are similar to values found for mammalian erythrocytes. Lateral diffusion in the cell membranes would account for the lipophilic pathway permeability just as well as diffusion across the cell membranes.