A substance P antagonist has recently been reported to have clinical efficacy in the treatment of depression. We have therefore analysed sections from human pons, including the raphe region, with double in situ hybridization using riboprobes complementary to substance P and the 5-hydroxytryptamine transporter (5-HT-T mRNAs). A distinct overlap of cell bodies expressing these two markers was observed in the dorsal and median raphe nuclei. Analysis of double-labelled sections revealed that almost half of the 5-HT neurons in the dorsal raphe and around 25% in the median raphe nucleus expressed substance P mRNA. The highest percentage was observed in the ventrolateral dorsal raphe nucleus and the lowest in the caudal raphe nucleus. These results demonstrate that the phenotype of the raphe 5-HT neurons varies between species, since so far no 5-HT-substance P co-existence has been demonstrated in the dorsal raphe complex of rat. The question is raised whether the present results may be of significance for understanding a possible role of substance P in depression.