Damage to the medial region of the thalamus, both in clinical cases (e.g., patients with infarcts or the Korsakoff's syndrome) and animal lesion models, is associated with variable amnesic deficits. Some studies suggest that many of these memory deficits rely on the presence of lateral thalamic lesions (LT) that include the intralaminar nuclei, presumably by altering normal function between the striatum and frontal cortex. Other studies suggest that the anterior thalamic nuclei (AT) may be more critical, as a result of disruption to an extended hippocampal system. Here, highly selective LT and AT lesions were made to test the prediction that these two regions contribute to two different memory systems. Only LT lesions produced deficits on a preoperatively acquired response-related (egocentric) working memory task, tested in a cross-maze. Conversely, only AT lesions impaired postoperative acquisition of spatial working memory, tested in a radial maze. These findings provide the first direct evidence of a double dissociation between the LT and AT neural aggregates. As the lateral and the anterior medial thalamus influence parallel independent memory processing systems, they may each contribute to memory deficits, depending on lesion extent in clinical and experimental cases of thalamic amnesia.Profound memory deficits including disruptions to allocentric (place-related) and egocentric (response-related) spatial information processing may occur following medial thalamic injury in humans (Holdstock et al. 1999;Kopelman 2002;Van der Werf et al. 2000, 2003. The source of these impairments is uncertain, with recent reports emphasizing either the intralaminar (ILn) or the anterior (AT) thalamic nuclei (Graff-Radford et al. 1990;Aggleton and Brown 1999;Harding et al. 2000;Mair et al. 2003). Damage to the AT in animal models mimics many of the allocentric spatial memory deficits associated with hippocampal system damage, which is believed to be a key indicator of episodic memory loss (