The main olfactory system of larval Xenopus laevis is made up of at least two subsystems consisting of subsets of olfactory receptor neurons (ORNs) with different transduction mechanisms. One ORN subset lacks the canonical cAMP transduction pathway and responds to amino acid odorants. The second subset has the cAMP transduction pathway but as yet suitable odorants are unknown. Here we report the identification of amines as proper olfactory stimuli for larval X. laevis using functional Ca(2+) imaging and slice preparations of the olfactory system. The response profiles of individual ORNs to a number of amines were extremely complex and mostly highly specific. The great majority of amine-sensitive ORNs responded also to forskolin, an activator of the olfactory cAMP transduction pathway. Most amine-induced responses could be attenuated by the cyclic nucleotide-gated channel inhibitor LY83583. This confirms that most amine-responsive olfactory receptors (ORs) are coupled to the cAMP-dependent transduction pathway. Furthermore, we show that trace amine-associated receptors (TAARs), which have been shown to act as specific ORs for amines in mammals, are expressed in the olfactory organ of X. laevis. The TAARs expressed in Xenopus cannot, however, explain the complex responses of individual ORNs to amines because there are too few of them. This indicates that, in addition to TAARs, there must be other receptor families involved in the detection of amines.