Changes in regional cerebral blood flow (rCBF) due to long-term abuse of opioids such as heroin or morphine are not yet fully understood in humans. The goal of the present study was to investigate rCBF alterations in a large sample of long-term opioid addicts in comparison to healthy controls. We investigated 21 opioid-dependent subjects, who were currently abusing heroin or were enrolled in a methadone or morphine maintenance program, and 36 healthy controls with <sup>99m</sup>Tc-HMPAO single photon emission computed tomography. We found a decrease in rCBF in most regions of interest in patients in comparison to controls. Long-term opioid dependence seems to decrease prefrontal CBF in particular. A right-greater-than-left CBF asymmetry in healthy subjects was reversed in patients. This change in CBF symmetry could reflect the different emotional status of opioid-dependent patients. Our findings are in line with neuropsychological investigations indicating a correlation of mood states with lateralization of hemispheric activation patterns.