1. Salt regulation was studied in blue crabs living at Na+ and Cl− concentrations of 1.5 to 3.0 meq·l−1. The crabs maintain blood Na+ at 302±36 meq·1−1 (±S.D.) and Cl− at 297±22 meq·1−1. 2. The transepithelial potential (TEP) across the whole crab is normally −2 to −4mV. Its response to changes in external Na+, K+, and Cl− is negligible, but values as large as −30mV were observed in Ca-free media. 3. Unidirectional fluxes are large, averaging 688±50 μeq·100 g−1·h−1 (±S.E.) for Na+ influx and 961±74 μeq·100 g−1·h−1 for Cl− influx in animals in net salt balance. 4. The responses of TEP and efflux to changes in external Na+ and Cl− indicate that about 50% and 70% respectively, of the effluxes meet the usual criteria for exchange diffusion. 5. The urine was nearly isosmotic with blood. Radioisotope data and a kinetic simulation model were used to estimate the rate of urine production as 12.7% of body weight per day. This represents approximately 26% of the total Na+ and Cl− efflux. 6. Invasion of freshwaters by the blue crab is accomplished by activation of salt uptake mechanisms, with little apparent reduction in either osmotic water permeability or urinary salt loss.