Having recently demonstrated in separate studies that the T-cell cytokine, interleukin-2, induces the growth of the pituitary tumor cell line GH3 and that in the same cells, the estrogen receptor mediates the mitogenic effect of growth factors, we sought here to determine whether the estrogen receptor was involved in the response to interleukin-2. We demonstrate that under steroid and serum free growth conditions, the pure antiestrogen, ZM 182780, blocks the mitogenic response of GH3 cells to interleukin-2. Transfection studies with a reporter plasmid responsive to the transcriptionally active estrogen receptor show that even in the absence of ligand, the estrogen receptor in these cells is transcriptionally active and this can be increased by interleukin-2. Further studies on the two estrogen receptor regulated proteins, the progesterone receptor and prolactin, showing that the levels of these proteins were increased by exposure of cells to interleukin-2, support the idea of a cross-talk between the estrogen receptor and interleukin-2 signal transduction.