The non-selective serotonin (5-HT) receptor agonist meta-chlorophenylpiperazine (mCPP) has been reported to elicit symptoms in patients with obsessive compulsive disorder (OCD). MK-212, another non-selective 5-HT receptor agonist, does not seem to induce obsessive compulsive symptoms in OCD patients. The major pharmacological difference between mCPP and MK-212 is their affinity for the 5-HT(ID) receptor. The aim of this study was to explore the role of the 5-HT(ID) receptor in the pathophysiology of OCD, by using a challenge paradigm with the selective 5-HT(ID) receptor agonist sumatriptan (Imigran). A randomized, double-blind, placebo-controlled crossover challenge with sumatriptan (100 mg PO) was performed in 15 OCD patients. Neither the obsessive compulsive symptoms nor mood or anxiety symptoms changed significantly following sumatriptan administration as compared to placebo. Sumatriptan did induce a significant increase in plasma growth hormone (GH) levels. In the present study, no indication were found for the role of the 5-HT(ID) receptor in the pathophysiology of OCD. It should be noted, however, that sumatriptan does not readily pass the blood-brain barrier. Selective 5-HT(ID) receptors with better brain penetrating properties may shed more light on the role of this 5-HT receptor subtype in OCD.