This study was initiated to compare the temporal response of serum lipoprotein lipase-suppressing mediator (LSM) and tumor necrosis factor (TNF) in lipopolysaccharide (LPS) -infused or -injected rats. Serial blood samples were obtained over a 5-day period from rats implanted with vascular catheters. Control rats infused with saline exhibited no detectable LSM activity during the 5-day observation period. LPS administered either by injection or infusion (6 h or 5 d) resulted in detection of serum LSM and TNF activities during the early period of observation with the LSM temporal response (8 h) outlasting the TNF response (3 h). The LSM response lasted a little longer in LPS-infused rats than it did in injected rats, but in each case LSM activity was not detected in serum samples collected at or after 12 h post-LPS. Neither the duration nor the magnitude of the TNF response differed between LPS-infused vs. -injected rats. Despite similarities in the LSM and TNF pattern in all rats receiving LPS, lethality was greater in LPS-infused animals than it was in LPS-injected rats. The results indicate that differences in lethality between LPS-injected and -infused rats cannot be explained solely by a differential response of serum TNF.