Reconstitution experiments in the heterologous phase of nephrotoxic nephritis (HNTN) have shown that tissue injury is directly related to the number of polymorphonuclear neutrophils (PMN) infiltrating the glomeruli. Recent studies have indicated that endotoxin pretreatment in this model enhances tissue injury under certain conditions. The aim of this project was to investigate the relationship between glomerular PMN infiltration and tissue injury after endotoxin in HNTN. A dose of nephrotoxic globulin (NTG) that resulted in low levels of albuminuria was chosen. The administration of E. coli lipopolysaccharide (LPS) to Sprague-Dawley rats 24 h before the induction of HNTN resulted in the earlier appearance of larger numbers of glomerular PMN than in animals injected with nephrotoxic globulin alone (P less than 0.05 at 1/2 and 1 h). However there was no significant increase in albuminuria nor in renal histological damage. There was no difference in the amount or rate of glomerular deposition of the NTG or rat complement between the two groups of rats. The more rapid accumulation of glomerular PMN can, however, be accounted for by the LPS-induced activation of endothelium, since endotoxin was detected in the kidneys 24 h after the injection of LPS. No endotoxin was present in the serum at the time of injection of NTG. Thus we have demonstrated in a model of PMN-mediated tissue injury, that an increase in PMN influx is not necessarily associated with exaggerated injury.