The retinal pigment epithelium (RPE) plays a critical role in the regulatio of retinal and choroidal function in normal and disease states. Due to limited availability of human tissues, an in vitro cell culture system is desired. Therefore, we have developed and characterized the primary cell lines of human RPE from donor eyes obtained from eye banks. Using human RPE cell cultures as a model, we conducted investigations to examine the various roles of RPE in the pathophysiology of retinal disorders. Human RPE cultures secreted significant quantities of interleukin-6 (IL-6) and intercellular adhesion molecule-1 (ICAM-1) but not interleukin-1 (IL-1) in response to the stimulation by inflammatory mediators. Interferon ~ (IFN-~) exhibited synergistic effects in the secretion of IL-6 and ICAM-1 i the presence of suboptimal levels of tumor necrosis factor ` (TNF-`) or IL- Cellular expression of ICAM-1, mostly localized to intercellular junctions, as observed in RPE treated with TNF-` and IFN-~. There is a close correlation between IL-6 and ICAM-1 secretion and IL-6 and ICAM-1 mRNA levels, respectively, suggesting the regulation at the gene transcription. The responses of RPE to inflammatory mediators in IL-6 and ICAM-1 secretion was rapid and sustained in the presence of stimulants but reversed to control levels quickly upon withdrawal of the stimulants, indicating the reversibility of the responses of RPE to inflammatory signals. These resul show that RPE responds to inflammatory stimuli by increased cellular expression and secretion of IL-6 and ICAM-1, which may in turn perpetuate immune reactions in the pathogenesis and/or prevention of retinal and choroidal diseases.