We used the avidin-biotin complex immunoperoxidase technique to test the reactivity of the abnormal corneal accumulations with five different monoclonal antibodies that recognize specific determinants on keratan sulfate. Eighty-eight corneas from 67 patients with macular corneal dystrophy were immunolabeled with the antibodies. In 31 corneas the abnormal accumulations did not react with any of the antikeratan sulfate antibodies, but 18 corneas reacted with all of the antibodies. The remaining corneas reacted with various combinations of the antibodies. The data suggest that the accumulations in macular corneal dystrophy are not always identical and that keratan sulfate is present in some cases but not in others. Thus, based on differences in the storage material, macular corneal dystrophy appears to manifest heterogeneity with at least two distinct varieties: keratan sulfate negative (type 1) and keratan sulfate positive (type 2).