Administration of the serotonin agonist m-chlorophenylpiperazine to rats produced a dose-related hyperthermia. Pretreatment with the serotonin receptor antagonist metergoline totally abolished this response, whereas similar treatment with haloperidol, phenoxybenzamine, naloxone, clonidine, pindolol, propranolol, methiotepin, and ritanserin was ineffective. In studies investigating the modification of the response by antidepressant treatments both acute (3 day) and chronic (22 day) administration of the MAO inhibitor clorgyline, as well as the tricyclics clomipramine and imipramine, attenuated the hyperthermic response to m-CPP. These findings are discussed with regard to the specificity of m-CPP-induced hyperthermia and its subsequent modification by antidepressant treatments, in order to evaluate this model's use as a probe for assessment of the serotonergic system.