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Most of the cloned serotonin (5-HT) receptor subtypes are present on enteric neurons that control gastrointestinal function. Because of the wide distribution of 5-HT receptor subtypes in the gut, the precise actions of currently marketed drugs are unclear. Furthermore, efficacy of these drugs varies between individuals. Two recent advances provide important potential explanations for this phenomenon: polymorphisms have recently been discovered in the gene for the key enzyme in neural 5-HT production, and physiologically relevant 5-HT4 receptor splice variants have been shown to be differentially located across intestinal regions. Functional 5-HT7 receptors have recently been demonstrated in the gut and, together with the 5-HT1A receptor, offer new therapeutic options. In addition, recently suggested identities for the elusive 5-HT1P receptor could result in other, more effective therapeutic targets.