Proliferative centers appear a possible mechanistic pathway of evolutionary change involving anterior pituitary adenomatous transformation. It appears significant that although pituitary adenomas are monoclonal and apparently unrelated to hyperplasia, there evolves a series of multistep transformations in the generation of excessive hormonal secretory activity. It is in terms of glandular and cellular secretion that one would recognize anterior pituitary adenomas largely as proliferative centers that predetermine clonality of cell multiplication. It might be largely because of change arising in the setting of initially established proliferative centers that subsequently respond in a feed-forward fashion to hormonal influences that secretory activity would prove determinant in the establishment of clones of adenomatous cells. It is in the setting of evolving selectivity in cell proliferative centers that involves assumption of secretory activity that hormonal feed-forward effects subsequently evolve as autonomous cellular propagation of both proliferative and secretory activity. Anterior pituitary adenoma is an alternative pathway to hyperplasia in terms of autonomous proliferative centers clonally selected in terms not only of cell division but particularly of secretory responsiveness to hormonal effect.