The polar compound hexamethylenebisacetamide (HMBA) is a differentiating agent in the murine erythroleukemia cell system (MELC). It induces, like dimethylsulfoxide, the commitment to terminal differentiation leading to a recovery in the expression of several genes like the globin gene. This molecule which also induces differentiation in other cellular types is a growth agent for human, ovine and porcine thyroid cells. Forty-eight hours after the onset of culture, porcine thyroid monolayer cells do not respond to thyrotropin (TSH) We demonstrate that a pretreatment from the onset of culture with HMBA of porcine thyroid cells prevents the loss of TSH-sensitivity. The TSH-sensitivity is concentration-dependent in HMBA and leads to the reorganization of cells into follicles, even in the presence of HMBA. However, the withdrawal of HMBA when TSH is added is absolutely required to obtain a total recovery in iodide trapping and organification. If HMBA is present during TSH-stimulation, it inhibits iodide trapping partially but iodide organification completely.