Morphologic alterations of the extracellular matrix in diabetes include thickening of the basement membrane and, as evidenced in the corneal epithelium, a decrease in the area of the basal cell membrane occupied by hemidesmosomes. To determine if the abnormal basement membrane in diabetes has altered epithelial recognition of sites for hemidesmosome formation and if diabetic epithelium can recognize sites for hemidesmosome formation on normal basement membrane, we recombined epithelial sheets and corneal stromas with denuded basement membranes in vitro using diabetic and control corneas. In recombinations of diabetic epithelium on normal stromas, the area of the basal cell membrane occupied by hemidesmosomes was 10.7%, significantly less than control recombinations (19.5%). Similarly, in recombinations of normal epithelium on diabetic stromas, the value (8.6%) was significantly decreased from control. These data may indicate altered cell-extracellular matrix interactions in diabetes.