The number of peripheral blood mononuclear cells (PBMC) producing IgA, IgG and IgM spontaneously, after in vitro polyclonal stimulation with pokeweek mitogen (PWM) and in response to autologous mixed lymphocyte reaction (AMLR), were determined by a protein A hemolytic plaque assay in 23 patients with IgA nephropathy confirmed by renal biopsies and in 24 normal controls. The geometric mean of circulating IgA-producing cells in Berger's disease (689 +/- 1.73 cells/10(6) PBMC) was increased when compared with the normal controls (332 X divided by 1.52 cells/10(6) PBMC; p less than 0.001). To a lesser degree, there was also an increase in the number of IgG-secreting cells (98 +/- 3.97 cells/10(6) PBMC vs. 38 +/- 2.90 cells/10(6) PBMC; p less than 0.05). After PWM stimulation, although the number of IgA-producing cells was increased in patients with IgA nephropathy, no significant differences were observed between the 2 groups. In response to AMLR, the number of IgA-secreting cells was significantly higher in the cases with Berger's disease (1,979 +/- 1.76 cells/10(6) non-T cells vs. 783 +/- 1.95 cells/10(6) non-T cells; p less than 0.001). Although it did not reach statistical significance, the patient group had also an increase in the number of IgG-producing cells (884 +/- 2.64 cells/10(6) non-T cells vs. 317 +/- 5.05 cells/10(6) non-T cells). These data support the existence of some abnormalities in the mechanisms regulating the synthesis of IgA in Berger's disease which might contribute to its pathogenesis.