Seminal work in Gary Van Hoesen's laboratory at Iowa in the early 1980s established that the hallmark neuropathology of Alzheimer's disease (AD; neurofibrillary tangles) had its first foothold in specific parts of the hippocampal formation and entorhinal cortex, effectively isolating the hippocampus from much of its input and output and causing the distinctive impairment of new learning that is the leading early characteristic of the disease (Hyman et al., 1984). The boundaries and conditions of the anterograde memory defect in patients with AD have been a topic of intense research interest ever since (e.g., Graham and Hodges, 1977; Nestor et al., 2006). For example, it has been shown that patients with AD may acquire some new semantic information through methods such as errorless learning, but learning under these conditions is typically slow and inefficient. Drawing on a learning paradigm (a collaborative referencing task) that was previously shown to induce robust and enduring learning in patients with hippocampal amnesia, we investigated whether this task would be effective in promoting new learning in patients with AD. We studied five women with early-stage AD and 10 demographically matched healthy comparison participants, each interacting with a familiar communication partner. AD pairs displayed significant and enduring learning across trials, with increased accuracy and decreased time to complete trials, in a manner indistinguishable from healthy comparison pairs, resulting in efficient and economical communication. The observed learning here most likely draws on neural resources outside the medial temporal lobes. These interactive communication sessions provide a potent learning environment with significant implications for memory intervention. J. Comp. Neurol. 521:4356–4369, 2013. © 2013 Wiley Periodicals, Inc.