The present study examined the comparative distribution of 5-HT1A receptor mRNA and 5-HT1A receptors in rat brain using a combination of in situ hybridisation histochemistry and in vitro receptor autoradiography. 5-HT1A mRNA was visualized using a 910 bp cRNA probe synthesised from a BalI-PvuII fragment of the rat 5-HT1A reetor gene, while 5-HT1A receptors were labelled with the 5-HT1A-selective ligand 8-OH-DPAT. In general terms, there was a complementary distribution of cells expressing 5-HT1A receptor mRNA and 5-HT1A receptor sites. High levels of both 5-HT1A mRNA and 5-HT1A receptors were evident in the hippocampal formation (CA1, CA3, dentate gyrus), entorhinal cortex, and raphe nuclei and lower levels in neocortex and thalamus. Although 5-HT1A mRNA was not expressed in any regions which did not also exhibit 5-HT1A receptors, within both the diagonal band and the medial septal nucleus mRNA levels were proportionately higher than 5-HT1A receptor levels, possibly reflecting receptor transport or a heterogeneity in 5-HT1A receptor turnover mechanisms. 5-HT1A receptor mRNA and 5-HT1A binding sites were undetectable in caudate/putamen and cerebellar regions. The present data indicate the synthesis of 5-HT1A receptors both in raphe serotonergic cells and anatomically specific serotonergic projection areas, further supporting both a presynaptic autoregulatory and postsynaptic modulatory role for this receptor in serotonergic transmission.