The calcium permeability of the mouse muscle nicotinic ACh receptor (nAChR) was determined using patch-clamp techniques. Single-channel currents were measured in pure external calcium and in mixtures of calcium with cesium or sodium. At low concentrations, calcium decreases the current carried by the monovalent cation. At higher concentrations, calcium displaces the monovalent cation as the main current carrier. In pure external calcium, the conductance of the nAChR is similar to the conductance of the NMDA receptor or the L-type Ca channel. With pure 110-mM calcium as the external cation, the slope conductance of the nAChR channel at negative potentials is 12 pS. An ion-permeation model based on the structure and function of the channel describes the currents. The ion-permeation model predicts that calcium contributes about 2% of the total inward current through a nAChR channel in physiologic solution. The current is about 7% of the calcium current through an L-type Ca channel. Because nAChRs are densely packed at the neuromuscular end plate, the calcium influx at an active synapse is expected to produce a locally high-calcium environment.