Observations in experimental animals and in humans have shown that the rate of progression of renal disease is influenced by gender. Deterioration of renal function in patients with chronic renal disease is more rapid in men than in women, independent of differences in blood pressure or serum cholesterol levels. In addition to genetically determined differences between the sexes in renal structure and function, sex hormones may directly influence many of the processes implicated in the pathogenesis of renal disease progression. Potential mechanisms include receptor-mediated effects of sex hormones on glomerular hemodynamics and mesangial cell proliferation and matrix accumulation as well as effects on the synthesis and release of cytokines, vasoactive agents, and growth factors. In addition, estrogens may exert potent antioxidant actions in the mesangial microenvironment, which may contribute to the protective effect of female gender.