We measured regional cerebral blood flow (rCBF) with the xenon 133 (133Xe) inhalation method and with regional cerebral uptake of technetium 99m d,l-hexamethyl propyleneamine oxime (99mTc-HMPAO) by single-photon emission computed tomography in 10 adult male patients with obsessive-compulsive disorder (OCD) and in 10 age-matched adult male normal controls. With the 133Xe method, there were no significant differences in cortical or basal ganglia blood flow between the patients with OCD and their matched controls. In the patients, there was a positive relationship between rCBF and the severity of both obsessive and compulsive symptoms (average r = .48). These rCBF findings were consistent with those of earlier reports of increased rCBF in patients with OCD who were undergoing imaginal flooding and who had exacerbation of symptoms following m-CPP administration. 99mTc-HMPAO is a lipophilic molecule that crosses the blood-brain barrier and is converted to a hydrophilic form that is trapped in the brain. The amount that is trapped is determined primarily by blood flow, but also by membrane permeability and kinetics of conversion of the 99mTc-HMPAO to the hydrophilic form. Compared with their matched controls, the patients with OCD had significantly increased 99mTc-HMPAO uptake in the high dorsal parietal cortex bilaterally, in the left posterofrontal cortex, and in the orbital frontal cortex bilaterally. Possible explanations include (1) increased rCBF that was not detected with 133Xe, (2) increased permeability of the blood-brain barrier and/or cell membranes, and (3) increased conversion and trapping of the lipophilic, injected form of 99mTc-HMPAO in these regions.(ABSTRACT TRUNCATED AT 250 WORDS)