Programmed cell death (apoptosis) is involved in glomerular injuries leading to glomerulonephritis. Bcl-2 and Fas are proteins that promote cell survival and death, respectively. This study tests the hypothesis that lupus nephritis is associated with alterations of Bcl-2 and Fas protein expression. Thirty-six patients with lupus nephritis and 10 controls (normal individuals) were included in this study. Bcl-2 and Fas positive cells were examined in kidney biopsies by immunohistochemistry. Bcl-2 and Fas serum levels were evaluated by enzyme-linked immunosorbent assay (ELISA). In the glomeruli of normal kidneys, Bcl-2 and Fas proteins were completely absent. In lupus nephritis patients, glomerular expression of Bcl-2 and Fas was seen in mesangial cells (1.3 +/- 0.1 and 2.0 +/- 0.1 for Bcl-2 and Fas, respectively). Similarly, a statistically significantly higher Bcl-2 (217.1 +/- 85.9) and Fas (767.9 +/- 271) serum levels were found in lupus patients compared to controls (148.6 +/- 87, 550.3 +/- 91 for Bcl-2 and Fas, P < 0.05). A direct correlation between serum Bcl-2 and Fas and chronicity index was also found. Compared to normal controls, lupus nephritis is associated with glomerular expression and elevated serum levels of Bcl-2 and Fas proteins. These findings suggest possible roles for Bcl-2 and Fas in glomerular injury during evolution of lupus nephritis. The diagnostic, prognostic and therapeutic ramifications of our findings are open to further investigation.