In the guinea pig, a unilateral labyrinthectomy is followed by an initial depression and a subsequent restoration of the spontaneous activity in the neurons of the ipsilateral vestibular nuclei. In two previous works, we have established the time course of these changes in the alert guinea pig using electrical stimulation as a search stimulus to select the analyzed neurons. The latter criterion was important to capture the many ipsilateral neurons that are silent at rest during the immediate postlabyrinthectomy stage. Because it is known that a pathway originating from the vestibular nuclei on one side crosses the midline and functionally inhibits the activity of the vestibular nuclei on the other side, we investigated in the first part of this study the spiking behavior of the neurons in the vestibular nuclei contralateral to the labyrinthectomy using the same procedure as that used for the ipsilateral neurons. The spiking behavior of 976 neurons was studied during 4-h recording sessions in intact animals and 1 h, 1 day, 2 days, or 1 wk postlabyrinthectomy. Neurons selected according to the electrical activation criterion were classified further as type I (their firing rate increased during ipsilateral rotation), type II (their firing rate increased during contralateral rotation), or unresponsive. The resting activity of type I neurons, which was 38.1 +/- 20.9 spikes/s (mean +/- SD) in the control state, increased statistically significantly 1 h after the lesion (53.3 +/- 29.1 spikes/s) and remained at this level 1 wk later (56.0 +/- 20.3 spikes/s). The sensitivity of type I units, which was 0.80 +/- 0.46 spikes/s per deg/s in the control population, decreased to 0.49 +/- 0.26 spikes/s per deg/s 1 h after the lesion and remained at this level 1 wk later (0.50 +/- 0.39 spikes/s per deg/s). When all monosynaptically activated neurons (type I, type II, unresponsive) were pooled, the sensitivity to horizontal rotation fell from 0.58 +/- 0.51 spikes/s per deg/s in the control state to 0. 15 +/- 0.25 spikes/s per deg/s 1 h after the lesion and to 0.20 +/- 0.32 spikes/s per deg/s 1 wk later. The major findings of the first part of this study in the alert guinea pig are thus in accord with those of Curthoys et al. and Smith and Curthoys in anesthetized guinea pigs. In the second part of this work, we studied the spiking behavior of the neurons in the vestibular nuclei after bilateral labyrinthectomy. After unilateral labyrinthectomy, the resting discharge of the ipsilateral monosynaptically activated vestibular neurons fell from 36.9 +/- 21 spikes/s (basal activity) to 6.7 +/- 17.0 spikes/s 1 h after the lesion and then recovered, reaching 17.4 +/- 18.9 and 40.8 +/- 23.7 spikes/s 1 day and 1 wk after the lesion, respectively. These observations raise the two following questions. What are the relative contributions of the loss of the excitatory influence from the ipsilateral labyrinth (destroyed) and of the persistence of the inhibitory influence from the contralateral labyrinth (intact) in the labyrinthectomy-induced depression of activity? And are the left-right asymmetries caused by a unilateral labyrinthectomy the driving force for restoration of activity? Here, we addressed these two questions by studying the spiking behavior of 473 second-order vestibular neurons in the alert guinea pig after a bilateral labyrinthectomy. In the acute stage, 1 h after bilateral labyrinthectomy, the resting discharge of the second-order vestibular neurons was 16.2 +/- 22.4 spikes/s. From comparison with the results obtained in the acute stage after a unilateral labyrinthectomy, we inferred that the ipsilateral excitatory influence was between two and three times more powerful than the contralateral inhibitory influence. (ABSTRACT TRUNCATED)