To identify the balance of Th1/Th2 cytokine expression in the kidney and evaluate the difference in cytokine balance between patients with lupus nephritis WHO classes IV and V. The expression of the CD40 molecule on cultured human mesangial cells was assessed by flow cytometry after stimulation with interferon gamma (IFN-gamma) or other cytokines. Frozen sections of kidney tissue from 10 patients with lupus nephritis and two non-SLE patients (with minimal-change disease) were stained with monoclonal antibodies for interleukin (IL)-4, IL-10, IL-12, IFN-gamma, CD4, CD8, CD40, CD68 and CD40L. CD40 expression of cultured mesangial cells was up-regulated by IFN-gamma, but was not down-regulated in the presence of the Th2 cytokines IL-4 and IL-10. In the glomeruli, CD40 expression and the ratios of IFN-gamma-/IL-10-, IL-12-/IL-4- and (IFN-gamma+IL-12)/(IL-4+IL-10)-positive cells were significantly higher in class IV than in class V lupus nephritis (P < 0.05). Also CD40, IFN-gamma and the activity index derived from the renal biopsy were closely correlated. IFN-gamma may contribute to the pathogenesis of proliferative glomerulonephritis by the up-regulation of CD40 and the activation of the cellular immune response in human lupus.