The resolution phase of inflammation is being increasingly recognized as a dynamic multifaceted process whose components may be amenable to pharmacological manipulation for therapeutic gain. Here, we review evidence that the lipoxins (LX), a family of lipoxygenase-derived eicosanoids generated during cell-cell interactions within the vascular lumen, are potential endogenous inhibitors of polymorphonuclear neutrophil (PMN) recruitment during glomerular inflammation. LX are generated in nanogram quantities in kidneys of rats with Concanavalin A-ferritin (Con A-F) immune complex glomerulonephritis and of mice with acute nephrotoxic serum nephritis (NSN). PMN-platelet transcellular pathways appear to be the major route to LX formation in these settings, PMN donating the labile epoxide intermediate leukotriene A4 for conversion by platelet LX synthase to LXA4. Complementary approaches using monoclonal antibodies and gene knockout suggest that PMN-platelet adhesion through P-selectin promotes transcellular LXA4 biosynthesis in vitro and in vivo. In support of a modulatory role in PMN trafficking; LXA4 and LXB4, the LX generated in greatest quantities by mammalian cells, inhibit PMN chemotaxis, adhesion to endothelial cells, and migration across endothelium and epithelium induced leukotrienes and some other mediators in vitro. Exposure of PMN to LXA4 ex vivo attenuates their recruitment in Con A-F glomerulonephritis. Furthermore, PMN recruitment is exaggerated during NSN in P-selectin knockout mice, coincident with reduced efficiency of transcellular LXA4 generation and reduced renal LXA4 levels. Replenishment of platelet P-selectin by transfusion of null mice with wild-type platelets reverses this defect in LXA4 synthesis and approximates PMN infiltrates in null and wild-type animals. Against this background, LXA4 stable analogues have been designed that retain the biologic activity of native LXA4 in vitro and should be useful tools for probing the therapeutic potential of LXA4 in disease. In the presence of aspirin, endothelial cell cyclooxygenase II (COX-II) transforms arachidonic acid to 15R-hydroxyeicosatetraenoic acid which, in the context of PMN-endothelial cell interaction, is converted by PMN 5-lipoxygenase to 15-epi-LX. Intriguingly, these novel LX also attenuate PMN adhesion and transmigration in model in vitro systems. Together, these observations suggest that LX may not only play important regulatory roles in the "stop programs" of renal inflammation, but also contribute to the anti-inflammatory activity of aspirin and related inhibitors of COX-II.