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The 5-hydroxytryptamine_1B/1D(5-HT_1B/1D) antagonist 2′-methyl-4′-(5-methyl-[1,2,4]oxadiazol-3-yl)-biphenyl-4-carboxylic acid [4-methoxy-3-(4-methyl-piperazin-1-yl)-phenyl]-amide (GR 127935) and 5-HT_1A antagonistN-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide (WAY 100635) were used to assess whether hyperactivity induced by 3 mg/kg (+)-3,4-methylenedioxymethamphetamine [(+)-MDMA] is mediated by 5-HT_1B/1D and/or 5-HT_1A receptors. Activity in the periphery and center of an open field as well as rearing activity were measured in photobeam monitors. (+)-MDMA-induced peripheral and central activities were blocked by GR 127935 (0.3, 0.625, 1.25, and 2.5 mg/kg); central hyperactivity was blocked by 0.1, 0.3, and 0.625 mg/kg GR 127935. WAY 100635 (0.5–2 mg/kg) had little effect on (+)-MDMA-induced activity except for an enhancement of central activity …