Human stromal (fibroblast) cultures were established from random, normal corneas obtained from the International Eye Bank in Baltimore. Cultures were assessed for the expression of Class I, Class II, monocyte/granulocyte and T-cell antigens before and after treatment with gamma or alpha interferon (IFN), interleukin 2, and 4 beta-phorbol 12 beta-myristate 13 alpha-acetate (PMA). Class I (B2 microglobulin) and monocyte/granulocyte (Leu M-1) antigens were evident before induction, natural killer cell (Leu 7) antigens were transiently expressed, and Class II (HLA-DR, Leu 10) antigens were not expressed until after induction with gamma IFN. PMA reduced the numbers of cells positive for Leu M-1 while alpha IFN and interleukin 2 had no effect on antigen expression. Kinetic studies of HLA-DR induction indicated that as little as 12 hours exposure to gamma IFN was sufficient to initiate induction and that 30% of the population was still expressing HLA-DR 7 days after removal of gamma IFN. The inducible expression of Class II antigens following lymphokine exposure may play a critical role in rejection of allografted corneas.