The 5-hydroxytryptamine1B receptor is a serotonin receptor subtype which is expressed predominantly in the basal ganglia. It has been suggested to play a role in movement and appetite control as well as in certain pathological states such as migraine. The recent cloning of the 5-hydroxytryptamine1B gene as well as the discovery of a radioligand that labels in rodents 5-hydroxytryptamine1B and possibly 5-hydroxytryptamine1D alpha receptors (S-CM-G[125I]TNH2) allowed us to compare the distribution of the messenger RNA and of the protein in mouse brain sections. A high 5-hydroxytryptamine1B messenger RNA level is found in the caudate-putamen in medium spiny neurons that project to the globus pallidus and the substantia nigra. In contrast, no messenger RNA is expressed in the globus pallidus and substantia nigra although these structures reveal the highest level of 5-hydroxytryptamine1B binding sites. In the hippocampus, 5-hydroxytryptamine1B messenger RNA is localized in the cell bodies of pyramidal cells of the CA1 field while the protein is found predominantly in the dorsal subiculum, a projection zone for the CA1 pyramidal neurons. In the cerebellum, 5-hydroxytryptamine1B messenger RNA is expressed in the Purkinje cells, which display no receptor binding sites. Conversely, moderate binding is found in the deep nuclei of the cerebellum, the main projection zone of the Purkinje cells. 5-Hydroxytryptamine1B sites are also detected in the superficial gray layer of the superior colliculus and the lateral geniculate nucleus, brain regions containing the terminals of retinal ganglion cells. The soma of these ganglion cells express high levels of 5-hydroxytryptamine1B messenger RNA while no 5-hydroxytryptamine1B binding sites were found in the retina. This study demonstrates that the main brain regions, expressing 5-hydroxytrypamine1B messenger RNA contain low densities of 5-hydroxytryptamine1B binding sites. Conversely, the major projection areas of these anatomical structures do not express detectable levels of 5-hydroxytryptamine1B messenger RNA, but present a high density of binding sites. In addition, our data suggest that the distribution of the 5-hydroxytryptamine1D alpha binding sites is different from that of the 5-hydroxytryptamine1D alpha messenger RNA. These results together with previous lesion studies, indicate that the 5-hydroxytryptamine1B and possibly the 5-hydroxytryptamine1D alpha receptors are localized predominantly on axon terminals, while their expression is low or absent at the somatodendritic level. The 5-hydroxytryptamine1D alpha proteins might therefore contain an addressing signal allowing their transport toward nerve endings.(ABSTRACT TRUNCATED AT 400 WORDS)