Medial thalamic damage produces memory deficits in humans (e.g., Korsakoff's syndrome) and experimental animals. Both the anterior thalamic nuclei (ATN) and rostral intralaminar plus adjacent lateral thalamic nuclei (ILN/LT) have been implicated. Based on the differences in their main connections with other neural structures, we tested the prediction that ATN lesions would selectively impair acquisition of spatial location discrimination, reflecting a hippocampal system deficit, whereas ILN/LT lesions would impair acquisition of visual pattern discrimination, reflecting a striatal system deficit. Half the rats were first trained in a spatial task in a water maze before switching to a visual task in the same maze, while the remainder were tested with the reverse order of tasks. Compared with sham-operated controls, (1) rats with ATN lesions showed impaired place learning, but normal visual discrimination learning, (2) rats with ILN/LT lesions showed no deficit on either task. Rats with ATN lesions were also hyperactive when their home cage was placed in a novel room and remained more active than ILN/LT or SHAM rats for the subsequent 21 h, especially during the nocturnal phase. These findings confirmed the influence of ATN lesions on spatial learning, but failed to support the view that ILN/LT lesions disrupt striatal-dependent memory.