We studied the effects of 5-hydroxytryptamine (5-HT, serotonin) on the vertebrate neuronal somatic cell hybrid TCX11. We compared electrophysiological and pharmacological properties of the 5-HT response to those of the dopamine (DA) response. The cells developed delayed rectification and the ability to generate action potentials. Both 5-HT and DA caused graded depolarizations associated with increases in membrane conductance. The cells, however, were 10 to 100 times more sensitive to 5-HT than to DA. Responses to the amines desensitized during sequential or continuous application, and each neurotransmitter could desensitize the cell to a subsequent dose of the other neurotransmitter (cross-desensitization). Reversal potentials for both amines ranged from 0 to 15 mV from cell to cell, but on any given cell, the reversal potentials for 5-HT and DA were equal. We applied a variety of drugs, including classical DA and 5-HT antagonists, and found no drug that blocked the response to one amine without a similar inhibition of the response to the other amine. We conclude that, on the hybrid TCX11, there is a receptor that mediates a depolarizing response with a conductance increase after interaction with 5-HT and DA. Our data suggest that the receptor is best classified as a serotonin receptor.