Interleukin-6 (IL-6) is a peptide whose properties include the ability to activate T-lymphocytes, stimulate the secretion of immunoglobulin, induce neuronal differentiation, and trigger the release of acute phase proteins. We have detected IL-6-like activity in conditioned medium from cultured human retinal pigment epithelial (RPE) cells with a bioassay based on the ability of IL-6 to induce the proliferation of murine B-9 plasmacytoma cells. Biologic activity increased approximately 90-fold when the cells were cultured in the presence of IL-1 alpha (30 units/ml). Western blot analysis confirmed that conditioned medium from IL-1 alpha-stimulated RPE cells contained peptides with molecular weights ranging between 19,000 and 30,000 and reactive with antibody to IL-6. Finally, Northern blot analysis indicated that cells cultured in the presence of interleukin-1 contained a 1.2 kilobase transcript that hybridized to a cDNA probe specific for IL-6 messenger RNA. IL-6 peptide on Western blots and mRNA on Northern blots were undetectable unless cells were cultured in the presence of IL-1 alpha. Although IL-6 is synthesized by a variety of cell types, this report is the first to detect its synthesis by an eye-specific cell type. Furthermore, these observations indicate that retinal pigment epithelial cells respond to IL-1, a cytokine that previously has been implicated in ocular inflammation.