Pharmacological and electrophysiological studies provide evidence for the involvement of different nicotinic acetylcholine receptor isoforms in rat neocortical and hippocampal signal transduction. Yet, rather little is known on the cellular localization of these isoforms. With the availability of isoform specific nucleic acid probes and sensitive non-isotopic detection systems, nicotinic receptors can be studied on the mRNA level in individual neurons. In this way, we have paradigmatically studied the distribution of the alpha 3 and alpha 4 isoform mRNAs of the nicotinic receptor in the rat telencephalon. In the cerebral cortex, alpha 3 transcripts were mainly located in pyramidal neurons of layers V and VI and in some non-pyramidal cells in layer IV, while alpha 4 mRNA was detected in different types of neurons located in almost all layers. In the hippocampus, local distribution of both transcripts was comparable. Only very few labeled neurons were observed in the dentate gyrus. In the CA region, the specific mRNAs were detected in pyramidal perikarya and individual neurons in the strata oriens and lacunosum-moleculare. Our data show that the applied method is sufficiently sensitive and isoform-selective in order to study the differential expression of nicotinic receptors on the cellular level in the mammalian brain.