It has been known for over 60 years that social isolation of children and the young of some non-human primate species elicits agitated vocalizing and other active behavior, which eventually segues into a second, passive stage of depressive-like responding. How this transition occurs remains obscure. A leading hypothesis proposes that continued activation of the neural substrates underlying the vocalization response drives the onset of the passive stage. Guinea pigs also exhibit a 2-stage, active/passive response during isolation, and much of the identification of neural structures underlying the separation vocalization was based on studies of electrical brain stimulation in guinea pigs. We, therefore, asked whether repeated electrical stimulation of brain sites subserving the isolation vocalization would increase later depressive-like responding in guinea pigs. In Experiments 1 and 2, female guinea pigs with stimulating electrodes placed in the bed nucleus of the stria terminalis (BNST) and periaqueductal gray, respectively, were tested over 10 daily, 30-min trials. Stimulation of either site produced elevated levels of vocalizing, which diminished over repeated isolation trials. However, there was no increase in depressive-like responding either before or after subsequent trials, or during probe trials in which no stimulation was administered. In Experiment 3, stimulation of the BNST increased vocalizing during the first 30-min of the 3-h isolation period, but produced no increase in depressive-like behavior during the remainder of the trial. In sum, continued activation of brain sites underlying isolation vocalizations was not sufficient, in and of itself, to induce later depressive-like responding.