Although cisplatin is one of the most effective cancer drugs which is widely used in the treatment of various neoplasms, its side effects, especially vomiting may limit its use. It has been demonstrated that cytotoxic drugs lead to a sudden release of serotonin (5-HT). The following study was performed to determine the possible interactions of cisplatin with 5-HT receptors. In this study, the effect of pretreatment with cisplatin on the contractile response of guinea pig ileum to serotonin was investigated. The contractile response of ileal tissue to various agonists was recorded using a Bio-Science isotonic transducer and a model 400 MDR Washington oscilloscope. All drugs were diluted in distilled water and Tyrode's solution to achieve the desired concentration before being added to the organ bath. Statistical significance was evaluated using the t-test. It was found that serotonin produces a biphasic contractile response in the isolated guinea pig ileum. Addition of cisplatin (10^-7 M) in the organ bath did not affect the contractile response to 5-HT. Pretreatment of guinea pigs with cisplatin (10 mg/kg/day, i.p.) for two days only resulted in a reduction of the contractile response to low concentrations of 5-HT. Pretreatment with cisplatin did not affect the contractile response to acetylcholine. We conclude that cisplatin pretreatment results in the selective destruction of some 5-HT receptors other than the 5-HT₃ receptor.