Patients with Obsessive-Compulsive Disorder (OCD) have been shown to demonstrate blunted cortisol and prolactin responses along with an exacerbation of obsessive-compulsive symptoms in response to oral administration of the pharmacological probe, meta-chlorophenylpiperazine (mCPP). In an attempt to replicate these findings, mCPP was administered orally in the dose of 0.5 mg/kg body weight in a randomized double-blind design to 34 OCD patients who were either drug-naive or drug-free for a minimum period of four weeks. The cortisol and prolactin responses were contrasted with those of 18 drug-free healthy subjects. The OCD patients showed significantly blunted cortisol and prolactin responses to mCPP challenge as compared to normal subjects. However, mCPP did not produce any significant exacerbation of obsessive-compulsive symptoms in the patient group. The results are suggestive of a serotonin (5-HT) receptor hyporesponsivity in the HPA axis. Even though previous studies indicate a hyperresponsivity of the 5-HT receptor system in the orbitofrontal-striatal-pallido-thalamo-cortical pathway as shown by significant symptom worsening following serotonergic challenge, the present study failed to replicate those results. 5-HT receptor hyporesponsivity in the HPA axis may be considered as a biological "trait marker" of OCD, and may not be directly involved in the mediation of symptomatology of the disorder.