Thyroid cultured cells are now used worldwide in clinical bioassays of TSH and of thyroid autoantibodies. Having originally developed the thyroid cell cultures (Ambesi-Impiombato et al. 1980) from rat glands in our laboratory, we now aim to improve the system, moving in two directions: a) TSH-independent mutants have been produced and characterized, which can be used in clinical bioassays without ''starvation'' from the hormone. b) Human cultures have been attempted using our experience with rat cells, as well as innovative strategies. Preliminary results now indicate that human normal differentiated cells may be available for clinical studies in vitro, when species-specific differences may be critical.