When guinea pig pups are isolated in a novel environment, they show an initial active phase of behavioral responsiveness characterized by vocalizations and locomotor activity. One earlier study found that after about an hour, pups began to exhibit a second, passive stage of responsiveness marked by a crouched stance, eye-closing, and extensive piloerection. The present experiments tested the hypothesis that the responses during the second, passive stage result from the isolation experience activating pathways underlying the acute phase response, i.e., that behaviors of the second stage represent “stress-induced sickness behaviors”. We found the following: (1) the passive stage did not emerge if pups remained with the mother during exposure to a novel cage; (2) injection of lipopolysaccharide, which induces an acute phase response, also led pups to exhibit crouching, eye-closing, and piloerection; and, (3) isolation in the novel cage produced a rise in rectal temperature, but did not affect peripheral or central levels of interleukin-1β (IL-1β)-immunoreactivity. Overall, these results are consistent with the notion that stress-induced sickness behaviors can account for some of the behaviors of isolated guinea pig pups, though if this is the case, cytokines other than IL-1β appear to be involved