Epidermal D-glucose transport was investigated in vivo in the brackish-water polychaete worm Nereis diversicolor. Transfer across the apical membrane is rate-limiting to D-glucose uptake, but the cuticle and/or mucus presents some resistance to D-glucose diffusion between bulk solution and transporting membrane. Maximal D-glucose influx is about 10(-12) mol sec-1 per cm2 of apical plasmalemma. Under natural conditions (approximately 1 microM D-glucose in the medium), backflux from the epidermal transport pool is negligible, but a significant paracellular outflux may occur. D-glucose influx across the apical membrane is Na+-dependent and completely inhibitable by phlorizin and harmaline; phloretin is less effective, and cytochalasin B has no effect. Influx is moderately depressed by KCN and iodoacetate, alpha-methyl-D-glucopyranoside is an effective substitute of D-glucose in transport. Animals acclimated to a low salinity, in which epidermal salt transport takes place, show a marked decrease of D-glucose transport capacity. On transfer of animals from a high to a low salinity, or vice versa, the corresponding change of influx occurs after a time-lag of at least an hour. Permeability of the epidermis to simple diffusion of D-glucose is 8 X 10(-8) cm sec-1 (on basis of gross epidermal area).