Sorbitol accumulation and transmembrane efflux in JS1 schwannoma cells were examined during osmotic stress in the presence of a sorbitol dehydrogenase (SD) inhibitor and following return to iso-osmotic conditions. SD inhibition promoted sorbitol accumulation under hyperglycemic and/or hyperosmotic conditions, and sorbitol efflux during iso-osmotic incubation was prevented by cooling to 4 degrees C or by quinidine. It appears that sorbitol levels in JS1 cells are dependent on SD activity and that sorbitol is rapidly removed upon restoring iso-osmotic conditions.