Male gender is associated with a more rapid progression of chronic renal disease. In various experimental models of renal injury, manipulation of the hormonal milieu can replicate the effects of gender on the course of renal disease. These observations suggest that sex hormones per se may be important determinants of the greater susceptibility of the male kidney to progressive renal injury. Sex hormones may influence many of the processes implicated in the pathogenesis of renal disease progression, including cell proliferation and the synthesis and degradation of collagen and proteoglycans. In addition, sex hormones may indirectly influence these processes by modulating the synthesis and release of vasoactive agents, cytokines, and other growth factors, which in turn are capable of altering mesangial cell function. Finally, estrogens also exert potent antioxidant effects that may contribute to the protective effect of female gender on the course of renal disease.