1. In mammals, unilateral labyrinthectomy induces an immediate depression of the resting discharges in the neurones of the ipsilateral vestibular nuclei. Later on, a spontaneous restoration of this activity occurs. The aim of the present study was to test the possibility that protein synthesis could be involved in the start of this process in the guinea-pig. 2. Cycloheximide (CHX), a protein synthesis inhibitor, was injected intramuscularly 1 h before (30 mg kg-1) and 5 h after (15 mg kg-1) labyrinthectomy. 3. In a first group of animals, CHX was found to induce an inhibition of protein synthesis at levels ranging from 71 to 93% for 9 h after labyrinthectomy. 4. In a second group of alert animals, we studied single unit activity of second-order vestibular neurones. It was found that, in the 12-16 h post-labyrinthectomy period, at a time when restoration began in guinea-pigs not treated with CHX, the discharges in the labyrinthectomized group treated with CHX were not different from those observed in a previous study in labyrinthectomized animals not treated with CHX. 5. We conclude that protein synthesis is not required for the start of restoration of activity in the vestibular neurones deprived of their ipsilateral labyrinthine input.