Rats with lesions to prefrontal cortex (PFC) or caudate nucleus (CN) were compared on tests of conditional associative learning (CAL) that placed varying demands on conditional rule learning and working-with-memory operations that are essential for response selection. Damage to either structure impaired performance, but the respective deficits resulted from disruption of different processes. CN lesions produced a consistent learning deficit that was thought to reflect a basic impairment in forming stimulus-response (S-R) associations. The behavior of PFC rats was more variable and depended on task requirements. When S-R learning or response selection was relatively easy, the PFC was not critical. However, when either component was made more difficult, thus requiring the contribution of strategic processes, PFC damage produced profound impairments. In addition to clarifying the roles of the PFC and CN in CAL, the results provide further evidence that multiple brain regions participate in relatively simple behavioral tasks and that their respective contributions can be dissociated.