In this study, the relationship between serum levels of IgA (s-IgA) and CD4 subsets in peripheral blood was investigated in patients with IgA nephropathy (IgA N). We have also recently reported that the percentage of CD4+ CD45RA+ cells was significantly decreased in this disease. Serum levels of immunoglobulins (IgG, IgA, IgM) and the percentage of CD4+CD45RA + cells or CD4+CD45RO + cells were measured by two-color analysis in blood samples obtained from 45 patients with IgA N, 30 patients with various glomerulonephritides and 30 healthy volunteers. A significant decrease of CD4+ CD45RA+ cells and a significant increase of CD4+CD45RO+ cells were observed in the IgA N group. Moreover, in the IgA N group, s-IgA correlated negatively with the percentage of CD4+CD45RA+ cells and correlated positively with that of CD4+CD45RO + cells. After 1 and 2 years, the same analyses were serially performed in 15 nonmedicated patients with IgA N. Similar results concerning the relationship between s-IgA and CD4 subsets were obtained both after 1 and 2 years. The percent changes of s-IgA (Delta s-IgA) correlated with Delta CD4+CD45RO + cells: r=-0.66483 (p<0.01) after 1 year, r=-0.69688 (p<0.01) after 2 years. On the other hand, Delta s-IgA correlated with Delta CD4+ CD45RA+ cells (p<0.05) after 1 year, but no after 2 years. It was concluded that s-IgA levels strongly correlate with the percentage of CD4+CD45RO + cells in peripheral blood, in patients with IgA N.