We investigated insulin-like growth factor (IGF)-I and -II mRNA expression in peripheral blood mononuclear cells (PBMC) and T cells obtained from 31 patients with IgA nephropathy (IgAN), 43 patients with other types of glomerulonephritis and 16 health age-matched controls. The majority of patients with IgAN showed elevated IGF-I and -II mRNA expression in PBMC, while no IGF-I and -II mRNA expression was detected in PBMC obtained from patients with other types of glomerulonephritis or normal controls. In T cells obtained from IgAN, other types of glomerulonephritis and normal controls, however, IGF-I and -II mRNA expression was not detected. A positive correlation was noted between IGF-I and -II mRNA levels and urinary protein excretion. IGF-I and -II mRNA expression also correlated with the histopathological findings in the renal tissue of patients with IgAN. Sixty-nine percent of patients with more than 1.0 g/day proteinuria showed strong [more than (++)] IGF-I and -II mRNA expression in their PBMC. Eighty-one and 76% of patients with grade III and IV histopathological findings, respectively, showed strong IGF-I and -II gene expression in their PBMC. We also studied the clinical course of 11 patients with IgAN during hospitalization. The IGF-I and -II mRNA levels in these patients decreased gradually, as did proteinuria, after treatment. These studies suggest that abnormal regulation of IGF-I and -II gene expression in PBMC may be associated with the progression of IgAN and may be useful as an indicator of disease activity.