The effect of carbamylcholine (Carb) on the release of(22)Na(+) by excitable microsacs is reversible: Carb does not promote an irreversible lysis of the microsacs. The microsacs form closed vesicles which are more permeable to water than to solutes present in physiological media; their apparent volume is controlled by the osmotic pressure of the medium in which they are equilibrated; they behave like micro-osmometers. In the presence of Carb, the apparent volume of the microsacs does not change: Carb has no significant effect on water permeability.The time course of(22)Na(+) release does not follow a simple exponential law and is fitted by a minimum of three exponentials. The complex kinetics are not due to electrical effects but presumably are caused by an heterogeneity both in size and in nature of the microsacs population.Microsacs at rest are permeable to(45)Ca(+),(42)K(+) and(22)Na(+), and to(36)Cl(-) but slightly or not at all to(32)S-SO -2 (4) . In the presence of Carb, the permeability to(22)Na(+),(42)K(+) and(45)Ca(++) increases, whereas the permeability to(14)C-tetraethylammonium and(14)C-choline does not change. Carb has no effect on the permeability to negatively charged or uncharged permeants.The kinetics of(22)Na(+) efflux is independent of the total concentration of Na(+) either inside or outside the microsacs. The outward transport of Na(+) thus varies only with the concentration of ion facing theinside of the membrane. Efflux of(42)K(+) follows the same laws as the efflux of(22)Na(+) except that it is blocked by(+)Na ions present in the outside medium.