Unilateral labyrinthectomy results in a syndrome of ocular motor and postural symptoms which abate over time in a process of behavioural recovery known as vestibular compensation. We have previously suggested that an increased Ca2+ influx in ipsilateral vestibular nucleus (VN) neurons at the time of the unilateral labyrinthectomy may exacerbate the depression of VN resting activity caused by the loss of excitatory input from the VIIIth nerve. In order to further test this hypothesis, we administered (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine hydrogen maleate (MK-801; 1.0 or 2.5 mg/kg i.p.), which blocks Ca2+ influx via NMDA receptor-mediated ion channels, to guinea pigs 0.5 h before unilateral labyrinthectomy and examined the effects on three symptoms of unilateral labyrinthectomy: spontaneous ocular nystagmus, yaw head tilt and roll head tilt. Pretreatment with MK-801 significantly altered the time course of the vestibular compensation of spontaneous nystagmus and yaw head tilt but had no significant effect on roll head tilt; in particular, 2.5 mg/kg MK-801 depressed spontaneous nystagmus frequency at 10 and 20 h post-labyrinthectomy relative to saline controls (P less than 0.05, post-hoc Scheffé F-test). The reduction in spontaneous nystagmus frequency was not simply a result of extended anesthesia, since other control animals, which received additional injections of the general anesthetic in order to achieve equivalent sleep times to the MK-801 group, did not show reduced spontaneous nystagmus frequency.(ABSTRACT TRUNCATED AT 250 WORDS)