The expression of MHC class II molecules is normally restricted to antigen presenting cells. Aberrant expression of class II molecules, however, was detected in the thyrocytes of autoimmune thyroid diseases. We attempted to regulate the expression of HLA-DR molecules in thyroid carcinoma cells by expressing the exogenous poly(ADP-ribose) synthetase gene. We transfected a metal inducible expression plasmid capable of expressing poly(ADP-ribose) synthetase gene into thyroid carcinoma 8505C cells and the transformants, treated with metal and IFN-gamma, were separated by Magnetic Cell Separation. The activity of the synthetase was increased in the HLA-DR-enriched transformants as compared with that in control or the HLA-DR+ transformants. RNA blot analysis and flow cytometric analysis revealed that the IFN-gamma-inducible expression of HLA-DR molecules was depressed by the induction of exogenous poly(ADP-ribose) synthetase gene. This result indicates that HLA-DR expression was correlated with the level of poly(ADP-ribose) synthetase in human thyroid carcinoma cells. Furthermore we examined the level of poly(ADP-ribose) synthetase in patients with autoimmune thyroid diseases. We observed a significant decrease in poly(ADP-ribose) synthetase in the patients. Taken together with the previous observation, the decrease in poly(ADP-ribose) synthetase is closely linked to the aberrant expression of HLA-DR molecules in some autoimmune thyroid diseases.