We have investigated the in vitro effects of interleukin-1-beta (IL-1-beta), interleukin-2 (IL-2), tumor necrosis factor-alpha (TNF-alpha), and interferon-gamma (IFN-gamma) on the induction of anti-thyroperoxidase (anti-TPO), anti-thyroglobulin (anti-Tg), and IgG-secreting cells (SC) by cultures of pokeweed mitogen (PWM)-stimulated peripheral blood mononuclear cells (PBMC) obtained from patients with Hashimoto's thyroiditis (HT), Graves' disease (GD), and controls (C). The effect of human thyroglobulin (Tg) together with cytokines was also studied. No differences in the numbers of PWM-induced IgG-SC were found. However, greater numbers of PWM-induced anti-TPO-SC were observed in the HT preparations compared to C, either with or without the addition of Tg (p < 0.05). Inhibition of numbers of IgG-SC with certain cytokines in all 3 groups of preparations was observed (0.01 < p < 0.05). Decreased numbers of anti-TPO-SC were noted in HT preparations after exposing cells to IL-2 and TNF-alpha. Induction of anti-TPO-SC after addition of Tg plus cytokines was significantly lower in HT than in the other 2 groups. In contrast, induction of anti-TPO-SC in C was markedly increased by all cytokines, which was enhanced by Tg. These data suggest that cytokines play a role in auto-antibody regulation in auto-immune thyroid disease (AITD).