The ventrolateral subdivision of the periaqueductal gray (vlPAG) and the adjacent dorsal mesencephalic reticular formation (dMRF) are involved in the modulation of active (rapid eye movement) sleep (AS). In order to determine the effects on AS of the suppression of neuronal activity in these regions, muscimol, a GABA receptor A (GABA(A)) receptor agonist, and bicuculline, a GABA(A) receptor antagonist, were microinjected bilaterally in guinea pigs and the states of sleep and wakefulness were examined. The main effect of muscimol was an increase in AS; this increase occurred in conjunction with a reduction in the time spent in wakefulness. The powerful effect of muscimol was striking especially when considering the small amount of naturally-occurring AS that is present in this species. Additional observable effects that were induced by muscimol were: 1) long lasting episodes of hypotonia/atonia during wakefulness and quiet sleep that included a lack of extensor tone in the hind limbs, and 2) frequently occurring cortical spindles, similar to those observed during naturally-occurring quiet sleep (sleep spindles), that were present during wakefulness. Conversely, bilateral microinjections of bicuculline induced a prolonged state of wakefulness and blocked the effect of subsequent injections of muscimol. These data suggest that endogenous GABA acts on GABA(A) receptors within the vlPAG and dMRF to promote AS in the guinea pig.