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A model of aspiration lung injury was developed in WT C57BL/6 mice to exploit genetically modified animals on this background, i.e., MCP-1(−/−) mice. Mice were given intratracheal hydrochloric acid (ACID, pH 1.25), small nonacidified gastric particles (SNAP), or combined acid plus small gastric particles (CASP). As reported previously in rats, lung injury in WT mice was most severe for “two-hit” aspiration from CASP (40 mg/ml particulates) based on the levels of albumin, leukocytes, TNF-α, IL-1β, IL-6, MCP-1, KC, and MIP-2 in bronchoalveolar lavage (BAL) at 5, 24, and 48 h. MCP-1(−/−) mice given 40 mg/ml CASP had significantly decreased survival compared with WT mice (32% vs. 80% survival at 24 h and 0% vs. 72% survival at 48 h). MCP-1(−/−) mice also had decreased survival compared with WT mice for CASP aspirates containing reduced particulate doses of 10–20 mg/ml. MCP-1(−/−) mice given 5 mg/ml …