Clinically, the hallmark of the human amnesic syndrome is an impaired ability to consciously recollect or remember daily events. If the medial region of the temporal lobes, including the hippocampus and related structures, is critical for establishing these new memories, then this brain region should be active whenever events are experienced, regardless of whether subjects are asked explicitly to learn and remember. Here we show that the medial temporal region is active during encoding and that the hemisphere activated and the amount of activation depend on the type of stimulus presented (objects or words), whether the stimulus can be encoded for meaning (real objects and words versus nonsense objects and words), and task experience (first versus the second time a task is performed). These findings demonstrate that the medial temporal lobe memory system is engaged automatically when we attend to a perceptual event and that the location and amount of activation depend on stimulus characteristics (physical form, meaning) and experience.