IgM mesangial nephropathy (IgMN) is a common pathologic finding in Taiwanese children with nephrotic syndrome. The hallmarks of IgMN are mesangial hypercellularity and IgM immune complex deposition in the mesangial area. In order to investigate whether the interleukin-6 (IL-6) and interleukin-1 (IL-1) protein production and gene mRNA expression are augmented in the local renal tissue of IgMN, we performed histobiochemical and mRNA studies using an immunopathologic technique and in situ hybridization. We also studied the correlation between urinary IL-6 levels and intensity of IL-6 expression in renal tissue. The results show that 15 cases of IgMN had overexpression with the highest score of both IL-6 and IL-1 proteins and mRNA expression in glomerular mesangial cells and diffuse distribution throughout the glomerular mesangium and capillary, Bowman’s capsule, interstitium and renal tubule. In contrast, the patients with minimal change nephrotic syndrome and normal controls failed to show IL-6 and IL-1 mRNA overexpression. The urinary IL-6 levels of the patients with IgMN were highly correlated with the intensity of IL-6 protein expression in renal tissue. The higher the IL-6 overexpression, the higher was the rate of steroid resistance with focal sclerosis. These findings suggest that IL-6 and IL-1 mRNA amplification may play important roles in the pathogenesis of IgMN. The urinary level and degree of overexpression of IL-6 may serve as a prognostic paramete