During the response of vertebrate olfactory receptor cells to stimulation, Ca(2+) enters the cilia via cyclic nucleotide-gated channels and is extruded by Na(+)-Ca(2+) exchange. The rise in Ca(2+) concentration opens a Ca(2+)-activated Cl(-) conductance which carries most of the inward receptor current. The dependence of Ca(2+) extrusion upon external Na(+) concentration was studied by using the falling phase of the Ca(2+)-activated Cl(-) current following a brief exposure to the phosphodiesterase inhibitor IBMX to monitor indirectly the decay in intraciliary Ca(2+) concentration. External Na(+) concentration was reduced by partial substitution with guanidinium, an ion which permeates the cyclic nucleotide-gated channel but does not support Na(+)-Ca(2+) exchange. The time constant describing the decay in current following IBMX stimulation was surprisingly little affected by substitution of external Na(+), being substantially retarded only when its concentration was reduced to a third or less of its normal value in Ringer solution. When the cilia were returned to Ringer solution after a period in reduced-Na(+) solution, the time constant for the final decay of current was similar to that seen when returning immediately to IBMX-free Ringer solution. This observation suggests that Ca(2+) extrusion via Na(+)-Ca(2+) exchange dominates the falling phase of the response to IBMX, which can therefore be used to assess exchanger activity. Rate constants derived from the time constants for current decay at different external Na(+) concentrations could be fitted by the Hill equation with a K(d) of 54 +/- 4 mm and Hill coefficient of 3.7 +/- 0.4. The cooperativity of the dependence upon external Na(+) concentration indicates that at least three Na(+) ions enter for each exchanger cycle, while the high affinity for external Na(+) contrasts with the photoreceptor and cardiac exchangers. The functional importance of this observation is that the relative insensitivity of the Na(+)-Ca(2+) exchanger to external Na(+) concentration allows normal response termination even following partial dilution or concentration of the olfactory mucus.