Cocultivation of human corneal fibroblasts (CFB) with allogeneic peripheral blood mononuclear cells (PBL) induced a minimal lymphocyte proliferative response, even when the fibroblasts had been pre-treated with interferon-gamma (IFN-gamma) and were HLA-DR positive. IFN-gamma-treated CFB did not express detectable HLA-DQ alloantigens. Cocultivation of CFB with PBL in the presence of Concanavalin A (Con A) or Phytohemagglutinin inhibited mitogen-induced lymphocyte proliferation by 40-90% relative to PBL cultured without CFB. Induction of HLA-DR expression on the CFB did not alter their inhibitory properties. Addition of indomethacin to cultures reversed the effect of CFB on Con A responses. However, no difference between proliferative responses to HLA-DR positive or negative CFB was seen in the presence of indomethacin. This weak response to induced Class II alloantigens on CFB suggests that induction of Class II alloantigens on corneal stroma alone may be insufficient to sensitize a recipient for Class II alloantigen-driven corneal graft rejection.