TSH, IGF-1 and cellular ras genes have been proposed to function in thyroid cell transformation. Using cultured follicular cells, we demonstrate that TSH, IGF-1 and microinjected activated ras protein individually stimulate DNA synthesis. TSH-stimulated pathways include Gs at the plasma membrane and cyclic AMP response elements in the nucleus. The pathways and nuclear targets of IGF-1 and ras action appear at least partially distinct from those used by TSH.