Nucleated erythrocytes of the blood clam, Noetia ponderosa, recover cell volume after a hypoosmotic stress by an efflux of K+, Cl- and taurine. When the cells are exposed to ionomycin followed by hypoosmotic stress, swelling is less and volume recovery is both faster and more complete than in control cells without the ionophore. The improved volume recovery is caused by a large increase in the efflux of taurine. The taurine efflux is altered by changing Ca2+ concentrations in the presence of the ionophore. Potassium regulation by the osmotically stressed erythrocytes is also increased in the presence of ionomycin, but only by a small amount, perhaps accounting for the initial decrease in swelling. Variation of Ca2+ in the presence of ionomycin without osmotic stress produces no change in the regulation of either osmolyte. These results indicate that both the osmotic stress and an increase in [Ca2+]i are required for the permeability change that produces taurine efflux.