Résumé : The role of the two different isozymes of the cAMP‐dependent protein kinase is still unclear. We have investigated the potential roles for each isozyme in dog thyroid cells, a model in which the function, expression of differentiation and proliferation are positively regulated by thyrotropin acting through cyclic AMP. The dog thyroid contains both type I and type II cAMP‐dependent protein kinases. These isozymes were selectively activated in vitro by type‐I‐directed and type‐II‐directed analog pairs. In thyroid slices, both type‐I directed and type II‐directed analog pairs synergistically activated thyroid hormone synthesis, as measured by incorporation of 131I into proteins and thyroid hormone secretion as determined by the release of butanol‐extractable 131I. In primary cultures of dog thyroid cells both isozyme‐directed analog pairs synergistically enhanced iodide trapping, a marker of differentiation, and DNA synthesis, as measured by the percentage of cells incorporating [3H]thymidine into their nuclei. However, DNA synthesis was more sensitive to type‐I‐directed pairs. The results demonstrate that both cAMP‐dependent protein kinase isozymes can mediate the action of cAMP on function, differentiation expression and cell proliferation in dog thyroid cells.