The effects of interferon-gamma (IFN-gamma) on the morphology of thyroid follicles and the expression of major histo-compatibility complex (MHC) class II antigens were examined. The thyroid follicles were suspended in RPMI-1640 containing 10% fetal calf serum with or without IFN-gamma (200 U/ml). After culture for 5 days, follicles were incubated in the presence of TSH (10 mU/ml) for 1 h and fixed for electron microscopic and immunohistochemical examination. Regardless of the presence of IFN-gamma, suspended follicles became inverted within 5 days. However, MHC class II antigens were expressed only in inverted follicles cultured with IFN-gamma. In inverted follicles cultured without IFN-gamma, TSH stimulation induced remarkable morphological changes, such as elongation of microvilli and an appearance of pseudopods. On the other hand, the follicles cultured with IFN-gamma showed poor response to TSH. Thus, IFN-gamma induced the expression of MHC class II antigens of cultured thyroid follicles and inhibited TSH-induced morphological changes in the cells.