The effect of two intravenous (i.v.) injections of low doses of lipopolysaccharide (LPS)(0.1 microgram/kg of body weight) administered at 7-day intervals on the systemic release of tumor necrosis factor (TNF) and interferon (IFN), on the rectal temperature, breathing and heart rate, and on packed cell volume (PCV), plasma glucose concentration, white blood cell (WBC) counts in 3-week-old calves, was estimated. The first injection of LPS caused a significant increase in breathing and heart rate, rectal temperature, prolonged hypoglycemia and leukopenia, but no significant changes in PCV were observed. TNF and IFN activity peaked at 2 h after LPS injection and disappeared from circulation by 4 h and 5 h, respectively. After the second injection of LPS, the reaction of calves was similar to that observed after the first injection, however, the breathing rate and TNF systemic production were significantly reduced. The results obtained indicate that a low dose of LPS leads to the development of 'late' tolerance manifested by hyporeactivity to TNF production but with maintained responsivity to IFN production, pyrogenic, hypoglycemic and leukemic response to the second injection of LPS. In conclusion, these results demonstrate that the tolerance response is not universal to all hematologic and immunologic parameters, and that the response needs to be evaluated with respect to the specific variable.