Carney Complex (CNC) is an inherited neoplasia syndrome characterized by spotty skin pigmentation, myxomas, endocrine tumors, and schwannomas. Among the endocrine tumors that comprise the syndrome, growth hormone-producing pituitary tumors are seen in approximately 10% of patients, although biochemical abnormalities of the growth hormone axis are much more common. In order to explore the role of loss of the CNC gene PRKAR1A on pituitary tumorigenesis, we produced a tissue specific knockout of this gene in the mouse. For these studies, we generated a mouse line expressing the cre recombinase in pituitary cells using the rat GHRH receptor promoter. These mice were then crossed with Prkar1a conditional null animals to produce tissue-specific knockouts. Although prolactinomas were observed in KO and control mice, the KO mice exhibited a significantly increased frequency of pituitary tumors compared to wild type or conventional Prkar1a^+/- mice. Characterization of the tumors demonstrated they were composed of cells of the Pit1 lineage that stained for GH, Prolactin, and TSH. At the biochemical level, levels of GH in the serum of KO animals were markedly elevated compared to controls, regardless of the presence of a frank tumor. These data indicate that complete loss of Prkar1a is sufficient to allow the formation of pituitary tumors and abnormalities of the GH axis, in close analogy to human patients with CNC.