We demonstrate that regions within human prefrontal cortex develop moment-to-moment models for patterns of events occurring in the sensory environment. Subjects viewed a random binary sequence of images, each presented singly and each requiring a different button press response. Patterns occurred by chance within the presented series of images. Using functional magnetic resonance imaging (fMRI), we identified activity evoked by viewing a stimulus that interrupted a pattern. Prefrontal activation was evoked by violations of both repeating and alternating patterns, and the amplitude of this activation increased with increasing pattern length. Violations of repeating patterns, but not of alternating patterns, activated the basal ganglia.