To understand the expression of inducible nitric oxide synthase (iNOS) and its possible association with apoptosis in human lupus nephritis, 48 renal tissue samples from patients with lupus nephritis were investigated immunohistochemically and by the terminal-deoxynucleotidyl-transferase-mediated dUTP nick end labeling method for the detection of iNOS and apoptosis, respectively. Modulation of apoptosis by p53 and Bcl-2 was also evaluated. This study showed immunohistochemical evidence of iNOS expression, predominantly in the glomerular and tubulointerstitial cells of class-IV lupus nephritis. The frequency of iNOS+ glomeruli was significantly correlated with that of apoptosis+ glomeruli, and the frequency of the latter was also significantly correlated with that of the glomeruli showing p53 overexpression. Bcl-2 was predominantly expressed in the cellular and fibrocellular crescents. This study suggests that induction of iNOS, and thus nitric oxide production, plays a role in the occurrence of apoptosis in the glomeruli of lupus nephritis; and the occurrence of apoptosis might in part be modulated by p53 and Bcl-2-related pathways. The expression of Bcl-2 in predominantly cellular and fibrocellular crescents suggests that Bcl-2 may participate in persistent proliferation of the crescentic cells.