Glomerular metalloprotease activity (phenanthroline inhibitable) was measured in cortical homogenates from rat kidneys by use of the rate of degradation of 3H-denatured type I collagen (gelatin). Glomerular metalloprotease activity was similar in male and female kidneys from kidneys from young (4 months) rats (27 +/- 7 and 34 +/- 6 micrograms of [3H]-gelatin degraded/h per milligram of glomerular protein, respectively). Glomerular metalloprotease activity was unaltered by age (18 to 20 months) in intact males but increased two times in old intact females. castrated males, and ovariectomized females. These aging changes correlated inversely with the level of age-dependent glomerular injury, i.e., old intact males had substantially greater glomerular damage than all other old groups. These observations suggest (1) that the androgens are a risk factor for the development of age-dependent glomerular damage: and (2) that an age-dependent increase in glomerular metalloprotease activity may protect against damage by limiting the build-up of glomerular extracellular matrix.