The partial serotonin agonist m-chlorophenyl-piperazine (m-CPP) has been reported to increase obsessive-compulsive symptoms in some patients with obsessive-compulsive disorder (OCD). The authors investigated the underlying physiological mechanisms of this variable exacerbation by imaging regional cerebral blood flow with the planar xenon-133 method after administration of oral m-CPP (0.5 mg/kg). Seven patients who responded to m-CPP with symptomatic exacerbation had a marked increase in global cortical perfusion (18.1%), in contrast to the remaining 7 nonresponders to m-CPP, who showed no change. These results suggest that m-CPP exacerbation of OCD symptoms is associated with increased cortical blood flow.