The structures that comprise the medial temporal lobe (MTL) have been implicated in learning and memory. The question of primary concern in the present research was whether the group of anatomically related structures (hippocampus, subiculum, presubiculum/parasubiculum, entorhinal cortex, perirhinal/postrhinal cortex) are involved in mediating a similar memory process or whether the individual structures are differentially involved in memory processes and/or in handling various types of information. A series of five experiments were carried out that involved selectively lesioning the main MTL structures and testing each animal on radial-maze tasks and procedures that provided measures of two different memory processes (reference memory, working memory) and the utilization of two kinds of information (spatial, nonspatial). The structures were found to differ functionally, with the hippocampus and the presubiculum/parasubiculum being especially involved in processing spatial information, and the perirhinal/postrhinal cortex having a specific role in remembering information over a brief time period (working memory). Lesions of the entorhinal cortex failed to affect consistently either memory process or type of information handled, but they did result in impairments in learning the complex spatial discrimination requiring reference memory and in working memory involving nonspatial information. The pattern of behavioral impairments resulting from damage to these discrete MTL structures suggests that several of the structures make unique contributions to learning and memory.