It is uncertain whether frequent marijuana use adversely affects human brain function. Using positron emission tomography (PET), memory-related regional cerebral blood flow was compared in frequent marijuana users and nonusing control subjects after 26+ h of monitored abstention. Memory-related blood flow in marijuana users, relative to control subjects, showed decreases in prefrontal cortex, increases in memory-relevant regions of cerebellum, and altered lateralization in hippocampus. Marijuana users differed most in brain activity related to episodic memory encoding.