Early life stressors have long been known to have powerful immediate and lasting biobehavioral consequences. Though much has been learned about the neural and endocrine substrates of such effects, increasing evidence suggests that elements of the immune system may also play a substantial role. Neonatal exposure to lipopolysacchride (LPS) has been found to affect later behavioral and endocrine endpoints in rats and mice in ways that parallel the effects of more-traditional early experiences. In guinea pigs—a rodent model for studies of filial attachment and separation—proinflammatory factors appear to contribute to the behavioral reaction of pups during isolation in a novel environment. Evidence for this assertion includes findings that: (1) exposure of guinea pig pups to LPS produces the same constellation of passive behavioral effects as does protracted isolation from the mother in a novel environment; (2) isolation in a novel environment increases proinflammatory cytokine expression and core body temperature; and, (3) administration of anti-inflammatory agents attenuate passive responses during isolation. Further, it appears that corticotropin-releasing factor (CRF) may activate the immune system during isolation since administration of this peptide increases the passive responses in the same way as does prolonged isolation or injection of LPS, and anti-inflammatory treatment attenuates the behavioral effect of CRF. These findings will be reviewed, and their implications for the understanding of early-experience effects and the development of psychopathology will be discussed.