Studies employing event-related potentials (ERPs) during tests of recognition memory have reported differences in neural activity elicited by new test items according to the specific demands of the retrieval task, such as retrieving studied words versus pictures. The present study investigated whether differential processing of new items is possible when retrieval demands vary unpredictably on a trial-by-trial basis. In separate study-test phases, subjects encoded lists of intermixed words and pictures, and undertook retrieval tests with words as test items. Each test item was preceded by a task cue that signaled whether subjects were to attempt to retrieve a word or a picture from the study list. In the “blocked”condition, the targeted study material remained constant throughout the test, whereas in the “mixed”condition, the targeted material varied unpredictably across trials. New-item ERPs were more positive-going when words rather than pictures were targeted in the “blocked” condition, replicating previous findings, but this effect was absent in the “mixed”condition. The findings are consistent with the hypothesis that differential processing of retrieval cues depends upon the adoption of different task sets (“retrieval orientations” that develop over multiple trials and cannot be adjusted merely in response to an instructional cue. Unlike the new-item ERPs, ERPs elicited by the task cues in the mixed condition differed according to targeted material, but only on trials when there was a switch between target material. The implications of these findings for understanding the different retrieval strategies engaged when retrieval demands are consistent versus inconsistent are discussed.