Summary:The bolus injection of tumor necrosis factor (TNF)/cachectin into rats has been reported to induce shock and tissue injury similar to catabolic states seen in cachexia. In the present study, we administered TNF/cachectin to rats by either bolus injection or slow infusion and analyzed the influence on splenocyte mitogen‐induced proliferation and interleukin‐1 (IL‐1) production. Also, TNF administration was compared with lipopolysaccharide (LPS) injection and saline injection. Serum TNF levels were elevated by 30 min following the start of slow infusion, peaked at around 90 min, and remained elevated throughout the 3‐h sampling. However, analysis of serum TNF following a bolus injection showed that TNF peaked earlier (30 min) but then declined over the next 2.5 h. LPS infusion resulted in a serum TNF peak at 60‐90 min with a rapid decline to near baseline by the end of the 3‐h sampling. Spleens were removed from rats following either 3 h of infusion or 3 h following bolus injection, and single‐cell suspensions were prepared and analyzed in culture for lymphocyte proliferation to either concanavalin‐A (con‐A) or pokeweed mitogen (PWM). Adherent spleen cell cultures were also tested for IL‐1‐forming capacity in response to LPS. The slow infusion of TNF had a suppressive effect on splenic T lymphocyte responsiveness to con‐A. This suppressive effect was not observed in the response to the T cell‐dependent B cell mitogen PWM. In contrast to slow infusion, TNF bolus injection had no effect on T lymphocyte mitogen responsiveness. LPS‐inducible IL‐1 production was augmented by TNF infusion and bolus injection. LPS infusion and saline infusion had no demonstrable effect on LPS‐inducible IL‐1 production by splenocytes. Also, TNF, by infusion and/or bolus injection, was not alone sufficient to increase IL‐1 production by splenocytes. These data suggest that the administration of TNF/cachectin to rats alters the activity of immunocytes in addition to previously reported metabolic alterations. Furthermore, the results suggest that the method of TNF/cachectin administration (bolus versus slow infusion) can affect the extent of immune cell alteration.