The host response to gram-negative endotoxin is characterized by an influx of inflammatory cells into host tissues, mediated in part by localized production of chemokines. In this study, using subtractive suppression hybridization analysis, we demonstrate that ANA-1 murine macrophages produce the CC chemokine, MIP-1 gamma, in response to LPS-mediated NO production. Gene transcription and protein translation are upregulated in the setting of LPS-induced NO synthesis. However, NO alone is a necessary but insufficient cofactor for induction of MIP-1 gamma protein expression; an NO-independent LPS signalling pathway is also required. This study suggests a novel mechanism by which NO modulates the host inflammatory response to endotoxin,