Chemokine production by resident fibroblasts contributes to the recruitment of migratory leukocytes to sites of tissue injury, The effects of cytokines on the expression of thymus- and activation-regulated chemokine (TARC), a potent chemoattractant for Th2 cells, were examined in cultured human corneal fibroblasts. The culture supernatants of cells incubated for 24 h in the absence or presence of either TNF-alpha (10 ng/ml) or IL-4 (10 ng/ml) alone did not contain TARC detectable by ELISA, However, exposure of cells to both cytokines resulted in marked release of TARC into the culture medium in a time-and dose-dependent manner. Similarly, quantitative RT-PCR analysis revealed that the two cytokines induced a synergistic increase in the amount of TARC mRNA in the cultured fibroblasts. This synergistic effect of TNF-a and IL-4 on TARC production by fibroblasts may contribute to the Th2 cell inflammation and consequent tissue damage associated with allergic inflammation.