Protein kinase C (PKC) inhibition attenuates ventilatory responses to acute hypoxia. Hypoxic ventilatory roll-off (VRO) could reflect underlying changes in PKC activity. Immunoblots of NTS lysates harvested at peak ventilation revealed subcellular translocations of particular PKC isoforms which coincided with PKC activity elevations. In contrast, reductions in PKC activity occurred during VRO, concomitant with selective decreases in PKCbeta and -delta translocation. Thus, alterations in PKC activity within the NTS which occur over time during hypoxia are isoform-selective and coincide with changes in ventilation.