Several studies have demonstrated that cerebellar deep nuclei, particularly the rostral fastigial nucleus (FNr), are involved in respiratory modulation. These nuclei receive inputs from the contralateral caudal inferior olivary nuclei of the medulla. The objectives of this study were to determine whether electrical and chemical activation of the vicinity of the caudal inferior olivary nuclei (vIOc) affected respiration and, if true, whether the FNr was involved in the vIOc stimulation-evoked ventilatory responses. Experiments were conducted in 30 anesthetized and spontaneously breathing rats. Our results showed that 1) electrical (25 or 100 microA at 10 or 20 Hz for 10 s) and chemical (1 or 100 mM, 25-50 nl N-methyl-D-aspartate) stimulation of the vIOc augmented ventilation predominantly via increasing tidal volume; 2) the responses to the electrical stimulation were almost eliminated by lesion of the contralateral FNr via microinjection of ibotenic acid; and 3) the respiratory responses to electrical stimulation in the vicinity of the rostral IO were 65-70% smaller compared with that evoked by vIOc stimulation. These findings strongly suggest that vIOc neurons play a significant role in modulation of respiratory activity, largely depending on their projections to the FNr.