Moth pheromones cause rises in intracellular Ca²⁺ concentrations that activate Ca²⁺-dependent cation channels in antennal olfactory receptor neurons. In addition, mechanisms of adaptation and sensitization depend on changes in cyclic nucleotide concentrations. Here, cyclic nucleotide-activated currents in cultured olfactory receptor neurons of the moth Manduca sexta are described, which share properties with currents through vertebrate cyclic nucleotide-gated channels. The cyclic nucleotide-activated currents of M. sexta carried Ca²⁺ and monovalent cations. They were directly activated by cAMP and cGMP, modulated by Ca²⁺/calmodulin, and inhibited by Lanthanum. M. sexta cyclic nucleotide-activated currents developed in an all or none-manner, which suggests that the underlying channels are coupled and act coordinately. At least one cAMP- and two cGMP-activated non-selective cation currents could be distinguished. Compared to the cAMP-activated current, both cGMP-activated currents appeared to conduct more Ca²⁺ and showed a stronger down-regulation by Ca²⁺/calmodulin-dependent negative feedback. Furthermore, both cGMP-activated currents differed in their Ca²⁺-dependent inhibition. Thus, M. sexta olfactory receptor neurons, like vertebrate sensory neurons, appear to express non-selective cyclic nucleotide-activated cation channels with different subunit compositions. Besides the non-selective cyclic nucleotide-activated cation currents, olfactory receptor neurons express a cAMP-dependent current. This current resembled a protein kinase-modulated low voltage-activated Ca²⁺ current.