The interactions of calcium-calmodulin with two fragments of the N-terminal domains of the olfactory alpha-subunit and rod beta-subunit cyclic nucleotide-gated channels have been investigated using nuclear magnetic resonance spectroscopy. The results indicate that in the two cases both the N-terminal and the C-terminal calmodulin lobes are involved in the interaction. The olfactory cyclic nucleotide-gated channel segment forms a 1:1 complex with calmodulin, whereas the rod fragment forms a 2:1 complex. The correlation times of the two complexes, as estimated by (15)N relaxation studies, are compatible with the observed stoichiometries. These results indicate differences in the mode of action by which calmodulin modulates the activity of both channels, and suggest either that the rod channel is modulated through a simultaneous interaction of two beta-subunits with calmodulin or that other regions of the N-terminus are necessarily implicated in the binding.