To evaluate the effects of desiccating ocular surface stress on the expression of chemokines and their receptors by the corneal epithelium and conjunctiva of C57BL/6 and BALB/c mice. Experimental dry eye was created in C57BL/6 and BALB/c mice. The concentrations of macrophage inflammatory protein 1alpha (MIP-1alpha), MIP-1beta, monokine induced by interferon (MIG)-gamma, and interferon-gamma-inducible protein (IP)-10 in the corneal epithelia and conjunctiva were measured by a multiplex immunobead assay. Expression of MIP-1alpha; MIP-1beta; regulated on activation, normal T-cell expressed and secreted (RANTES), MIG, IP-10; monocyte chemoattractant protein (MCP)-3; eotaxin-1; CCR5; CXCR3; and CCR3 in the cornea and conjunctiva were evaluated by real-time PCR and immunostaining. Desiccating stress significantly increased concentrations of MIP-1alpha, MIP-1beta, IP-10, and MIG proteins in the corneal epithelium and conjunctiva of C57BL/6 mice. Furthermore, it increased levels of MIP-1alpha, MIP-1beta, and CCR5 transcripts in the cornea and conjunctiva and RANTES, MIG, IP-10, and CXCR3 transcripts in the conjunctiva of C57BL/6 mice. In contrast, levels of MCP-3, eotaxin-1, and CCR3 transcripts increased in both tissues of BALB/c mice. In situ immunodetection of chemokines and their receptors was similar to their pattern of gene expression. Specific patterns of Th-1 and -2 chemokines and their receptors are induced in the mouse ocular surface by desiccating stress in a strain-related fashion. Desiccating stress potently stimulates the expression of Th-1 cell-attracting chemokines and chemokine receptors on the ocular surface of C57BL/6 mice.