This study's aim was to determine the early postoperative expression of proinflammatory cytokines interleukin-1 (IL-1) and tumor necrosis factor-alpha (TNF-alpha) by corneal grafts. BALB/c (n = 90) and C57BL/6 (n = 90) murine recipients were grafted with donor corneas from either syngeneic or allogeneic mice. At 7 and 14 days after surgery, corneal grafts were excised and the recipient rims separated from the donor tissue. Corneal segments were cultured and assayed for cytokines by enzyme-linked immunosorbent assay (ELISA). There was profound upregulation in expression of both IL-1alpha and TNF-alpha after corneal transplantation. Among both low-rejecting BALB/c and high-rejecting C57BL/6 hosts, levels of IL-1alpha were significantly (p < 0.01) more marked in allogeneic as compared to syngeneic grafts. TNF-alpha overexpression was similarly more marked in allogeneic as compared to syngeneic grafts in both BALB/c and C57BL/6 hosts, although the difference was generally more marked among high-rejecting C57BL/6 recipients. In the case of both IL-1alpha and TNF-alpha, the principal source of cytokine expression in the transplanted tissue was the recipient rim. There is significant overexpression of both IL-1alpha and TNF-alpha during the first 2 weeks after transplantation in both syngeneic and allogeneic orthotopic corneal grafts. However, whereas in syngeneic grafts cytokine expression generally decreases after the first postoperative week, significantly elevated cytokine levels are sustained in allogeneic grafts, implicating IL-1 and TNF-alpha as mediators of the alloimmune response in corneal transplantation.