The Na+ gradient has been implicated as the sole or primary energy source for accumulative transport of organic solutes (e.g., sugars, amino acids) across the mucosal membrane of a variety of epithelial cells. A basic question concerning the Na+-coupled transport process in epithelia is whether the energy available from the transmucosal Na+ electrochemical difference is sufficient to sustain an accumulated organic solute steady-state level. Measurements of Na+ activities, with Na+-sensitive microelectrodes, gave accurate estimates of the Na+ electrochemical potential difference across the mucosal membrane of Aplysia californica gut. The results suggest that the transmucosal Na+ gradient can furnish sufficient energy to sustain the observed intracellular levels of the cotransported species. Many other species sustain large intracellular-extracellular gradients (less than 10(6):1) of free solutes. Theoretical models suggest that secondary active transport mechanisms in these epithelia operate by energetic multiple coupling to the Na+ electrochemical gradient; coupling coefficients of approximately 3 may represent an evolutionary optimization of these epithelial cotransporters. To properly investigate the cotransport mechanisms and energetics in invertebrate membranes, prototype mammalian vesicle experiments should be extended to the invertebrate laboratory.