Sixteen patients manifested the syndrome of loss of environmental familiarity. The syndrome is characterized by an inability to recognize familiar surroundings in spite of relatively intact verbal memory, cognition, and perception. In addition to the loss of environmental familiarity, other clinical disturbances, including central achromatopsia, prosopagnosia, palinopsia, visual hallucinations, dressing disturbances, or impaired revisualization, were present in several cases. Radiologic studies revealed that all patients had right medial temporo-occipital lesions; three had additional left-sided lesions. Clinical observations suggest that the syndrome is a class-specific agnosia similar to prosopagnosia.