The involvement of 5-HT2 receptor subtypes in mediating a contraction response in the isolated intestine of Suncus murinus was investigated using DOI ((±)-1-(2,5-dimethoxy-4-iodophenyl)-2-amino-propane, a 5-HT2 receptor agonist) which produced a bell-shaped concentration response curve that was significantly (p<0.05) reduced by methysergide (a 5-HT1/2 receptor antagonist, 1 μM) but not ketanserin (a 5-HT2A receptor antagonist, 1 μM), yohimbine (a 5-HT2B receptor antagonist, 1 μM) or a combination of ondansetron (a 5-HT3 receptor antagonist, 1 μM) plus SB204070 (8-amino-7-chloro(N-butyl-4-piperidyl) methylbenzo-1,4-dioxan-5-carboxylate hydrochloride, a 5-HT4 receptor antagonist, 1 nM). The contraction response to the lower concentrations of DOI (10 nM–0.3 μM) was reduced in the presence of SB206553 (5-methyl-1-(3-pyridylcarbamoyl)-1,2,3,5-tetrahydropyrrolo[2,3-f]indole, a 5-HT2B/2C receptor antagonist, 1 μM), whilst conversely, the reducing response to the higher concentrations of DOI (1–30 μM) was prevented. A repeated challenge with 3 μM DOI produced a smaller response (desensitisation) and also reduced the response to 5-HT (5-hydroxytryptamine, 0.3 μM) that was inhibited by SB206553 (1 μM). Data indicate that 5-HT2C receptors are likely candidates to mediate the contractile response to DOI and demonstrate desensitisation to repeated challenges