Cyclic AMP (cAMP) is the second messenger that stimulates growth and differentiation of thyroid cells, which are dependent upon thyrotropin for the initiation of the cell cycle. Treatment of thyroid cells with phosphodiesterase inhibitors, such as 1-methyl-3- isobutytxanthine (IBMX), RO-20-1724, or aminophylline, induces persistent levels of cAMP and blocks cell proliferation. IBMX-treated cells are arrested at the G1- S border, but removal of the drug allows cell growth to resume. The inhibiting effect of IBMX is dose dependent, and the phase of the cell cycle is irrelevant. These data indicate that prolonged and steady accumulation of cAMP blocks the cell cycle in thyroid cells.