The effects of bilateral hippocampal and neocortical lesions were examined on acquisition and retention of classically conditioned responses based on (a) simple associations, (b) a nonconditional discrimination, and (c) a conditional discrimination in the same subjects. Results showed that combined hippocampal and neocortical damage permanently prevented (within the limits tested) both acquisition and retention of learned behavior based on the conditional discrimination but had no effect on behaviors based on the nonconditional discrimination or simple associations. Neocortical lesions alone had no effect on either conditional or nonconditional discriminative responding, but they did temporarily disrupt acquisition and retention of behavior dependent on CS-CS (two conditioned stimuli) associations. Neither lesion affected learned behaviors mediated by CS-US (conditioned stimulus and unconditioned stimulus) associations. Thus, results showed that hippocampal damage selectively disrupted learned conditional behaviors and also revealed that central nervous system control of conditional discrimination performance, within-compound associations, and CS-US associations is mediated by different neural mechanisms.