The production of cytokines and their receptors in the pituitary gland as well as receptor-mediated cytokine effects on pituitary function have been demonstrated. We have investigated whether the naturally occurring interleukin-1 receptor antagonist (IL-1ra), which has been shown to block IL-1 biological actions during inflammatory processes, could be expressed in human pituitary adenomas (n = 16) cultured in vitro. By polymerase chain reaction of reverse-transcribed RNA we detected IL-1ra messenger RNA in cultures of all types of pituitary adenomas under basal conditions as well as after stimulation of the cells with endotoxin or phorbol myristate acetate. The amplified complementary DNA fragment was identical to the fragment observed when RNA from purified human monocytes was subjected to reverse transcription polymerase chain reaction. In addition, we provide evidence that the IL-1ra messenger RNA detected in human pituitary adenomas corresponds to the intracellular IL-1ra variant. By using specific primers for the monocyte/macrophage marker CD14 as a control, we could exclude a contamination by monocytes or macrophages in the cell cultures of pituitary adenomas as a source of IL-1ra expression. Immunofluorescence studies showed the presence of cellular IL-1ra protein in the pituitary adenoma cultures and the colocalization with hormone-producing cells in GH- and ACTH-secreting adenomas. Production of IL-1ra within the anterior pituitary may act as a protective mechanism, modulating the sensitivity of pituitary cells to circulating or intrinsically produced IL-1 during inflammatory or tumoral processes.