In vitro immunoglobulin (Ig) synthesis using a co-culture technique after activation of lymphocytes with pokeweed mitogen, T-cell subsets and interleukin-2 (IL-2) production was studied in 10 children who suffered from IgM mesangial nephropathy (IgMN), 10 children who suffered from minimal change nephrotic syndrome (MCNS) with hypercellularity and 6 children who suffered from MCNS with normal cellularity during the acute nephrotic phase. Reduced in vitro IgG production was found in the presence of OKT8 cells from all groups of patients. However, in vitro IgM production was increased only in OKT8 cells from IgMN and MCNS patients with hypercellularity. In vitro Tac expression on the OKT8 cells, IL-2 production, T-cell subsets including Leu2a+15+ (suppressor T-cells), Leu2a+DR+ (activated suppressor T-cells) and Leu3a+8+ (suppressor T-cell inducer) were all increased in IgMN and MCNS patients with hypercellularity. There was a significant correlation between in vitro IgM production by co-culture technique and IL-2 production. These results strongly suggest the hyperfunction of isotype-specific suppressor T-cells which may affect the switch of IgM B-cells to IgG B-cells in IgMN and MCNS patients with hypercellularity and may be used to explain in part the clinical findings of lower serum IgG and increased IgM in those patients.