Lipopolysaccharide (LPS), an endotoxin associated with gram-negative bacteria, is a potent activator of the immune system. We have tested the effects of ICV infusions of LPS (10 ng) or Ringer's solution on the induction of the proto-oncogene protein c-Fos in the brain as well as plasma levels of corticosterone and splenic concentrations of norepinephrine (NE) and VIP. At 3 h post-ICV infusion of LPS, numerous labeled neurons were observed in the paraventricular nucleus (PVN) of the hypothalamus and the nucleus tractus solitarius (A2) region of the brain stem. Also, corticosterone and splenic NE and VIP levels were all elevated post-ICV LPS. Analysis of the time course for the induction of c-Fos protein in the brain following IP injections of LPS indicated that, relative to control injections, increased numbers of c-Fos-positive cells were detected in the PVN 0.5 h following IP injections (100 micrograms), peaked at 2-3 h postinjection, and then returned to control levels at later intervals. Additional dose-response data for IP LPS indicated a small increase in the number of labeled cells at a dose of 4.0 micrograms, and the number and staining intensity increased up to a dose of 100 micrograms. Corticosterone levels followed a similar pattern and were elevated at the 4.0 micrograms IP dose of LPS and increased to peak levels at 40 micrograms and higher. In contrast to ICV injections, splenic NE levels were unaltered by IP injections of LPS.(ABSTRACT TRUNCATED AT 250 WORDS)