Based on the finding that the mechanism of membrane protein sorting may be similar in neurons and epithelial cells, we have investigated the localization of the 5-hydroxytryptamine1A and 5-hydroxytryptamine1B receptors in Eli Lilly and Company canine kidney (LLC-PK1) cells (epithelial cells from pig kidney) stably transfected with the corresponding cDNAs. Receptors were characterized by radioligand binding, measurement of coupled adenylate cyclase activity and immunofluorescene with specific antibodies. Confocal microscopy and cell surface biotinylation experiments showed that the 5-hydroxytryptamine1A receptor, which is at the somatodendritic level in neurons, was targeted to the basolateral surface whereas the 5-hydroxytryptamine1B receptor, which is localized on nerve endings, predominated intracellularly. Such a difference in the localization of these two receptors suggests that the signal for the differential addressing of 5-hydroxytryptamine1A and 5-hydroxytryptamine1B receptors is contained within their primary sequence and confirms that epithelial cells can be used as a suitable model to study receptor targeting in neurons.