The aim of this study was to determine whether IGF-1 and INS are able to induce HLA-DR antigen expression (AgHLA-DR) in cultured human thyrocytes. Cytotoxicity assay in thyroid epithelial cells (cultured for 7 days to avoid spontaneous antigen expression) from 14 patients operated due to different thyroidal diseases, was used to assess HLA-DR expression. AgHLA-DR was reinduced adding IFN-delta, IGF-1 or INS to the culture media, alone, combined or associated with TSH or TBII. Both IGF-1 and INS induced HLA-DR expression in a similar way as IFN-delta did, and the response was enhanced with their combination, suggesting that they have different sites of action. Their association with TSH or TBII further augmented the response. To determine if IGF-1 acts via lymphocyte IFN-delta secretion, peripheral lymphocytes from 5 normal subjects were cultured with and without IGF-1 and the supernatant was used as stimulator, observing a stimulation similar to that induced by IFN-delta. This finding supports the hypothesis that IGF-1 acts stimulating a specific tyrosine kinase protein (p56 1ck) which is located in T lymphocyte receptors. According to our results we can conclude that, at least in vitro, both IGF-1 and INS play a role in the immune process, probably exerting a paracrine effect on autoimmunity, acting as perpetuating factors.