Patients with frontal lobe lesions were adminstered tests of paired-associate learning in which cue and response words are manipulated to increase interference across two study lists. In one test of paired-associate learning (AB-AC test), cue words used in one list are repeated in a second list but are associated with different response words (e.g., LION-HUNTER, LION-CIRCUS). In another test (AB-ABr test), words used in one list are repeated in a second list but are rearranged to form new pairs. Compared to control subjects, patients with frontal lobe lesions exhibited disproportionate impairment of second-list learning as a result of interference effects. In particular, patients exhibited the poorest performance during the initial trial of the second list, a trial in which interference effects from the first list would be most apparent. These findings suggest that the on-line control of irrelevant or competing memory associations is disrupted following frontal lobe lesions. This disruption may be indicative of an impaired gating or filtering mechanism that affects not only memory function but other cognitive function as well.