The trabecular meshwork cellularity (cells/unit tissue area) was compared in patients with primary open-angle glaucoma (POAG) with that of nonglaucomatous (NG) individuals. The NG specimens (n = 69) include specimens from the prenatal period (n = 14) as well as the postnatal period to age 98 years (n = 55). The glaucoma specimens (n = 49) covered a wide-range of ages (23-80 years) and were obtained at trabeculectomy (n = 31) or at autopsy (n = 18). Our results show that the trabecular cellularity in NG specimens decreases most rapidly and in a nonlinear manner in the late fetal period and for the first few years of postnatal life. This rapid decline in cellularity then slows down to proceed in a nearly linear manner for the remainder of the 98 years of life studied. The meshworks from patients with POAG have a lower cellularity than normals over the wide range of ages examined, but both types of specimens undergo similar declines in cellularity with age. Thus, the age-cellularity curves for both the NG and POAG specimens are parallel to each other. The loss of cells occurs in a gradient-like manner with the inner tissues being most affected and the outermost tissues least affected. A variety of statistical tests show that these changes in cellularity are highly significant and specific. These findings are compared to the loss of endothelial cells in the cornea and they are discussed in relation to the important clinical characteristics of POAG.