An important feature of the pulmonary inflammatory response is that the production of certain cytokines and chemokines is largely confined to the lung. This study investigated the local and systemic responses of macrophage inflammatory protein-2 (MIP-2) and cytokine-induced neutrophil chemoattractant (CINC) in rats administered with either intratracheal or intravenous lipopolysaccharide (LPS). Intratracheal LPS induced a significant increase in MIP-2 in bronchoalveolar lavage (BAL) fluid with no detectable MIP-2 in the plasma. In contrast, CINC was significantly increased in both BAL fluid and the plasma after intratracheal LPS challenge. Cell-associated MIP-2 was increased in the pulmonary-recruited neutrophils (PMNs) but not in the circulating PMNs in rats given intratracheal LPS. Cell-associated CINC was increased in both the recruited and circulating PMNs in these animals. Intravenous LPS caused a marked increase in plasma MIP-2 and CINC, whereas only a small elevation of both MIP-2 and CINC concentrations in BAL fluid was observed. The lack of CINC compartmentalization compared to MIP-2 implies that these C-X-C chemokines are regulated differentially and may have different effects upon polymorphonuclear leukocyte (PMN) recruitment into the alveolar space in response to intrapulmonary LPS or bacterial challenge.