In Graves' disease (GD) the presence of antibodies to the thyroid stimulating hormone (TSH) receptor leads to stimulation of the thyroid gland. The thyroid stimulating activity of Graves' IgG is normally ascertained by bioassays measuring cAMP production. We have investigated the effect of Graves' IgG on the quantitative activation of thyroglobulin (TG) gene in cultured human thyroid cells by RNA hybridisation. TG mRNA expression was activated by TSH and Graves' IgG. Nuclear transcription assays showed that the increase in cytoplasmic mRNA levels was due to increased transcription of TG specific mRNA in nuclei of thyroid cells. Whilst TSH led to a dose dependent increase in TG mRNA levels, Graves' IgG led to a variable activation of TG gene. A significant correlation between the increased TG mRNA transcription and cAMP production was observed with Graves' IgG. Thus the activation of the TG gene by Graves' IgG occurs in parallel with elevation of cAMP.