The decrease in brain CO₂ partial pressure (pCO₂) that takes place both during voluntary and during pathological hyperventilation is known to induce gross alterations in cortical functions that lead to subjective sensations and altered states of consciousness. The mechanisms that mediate the effects of the decrease in pCO₂ at the neuronal network level are largely unexplored. In the present work, the modulation of gamma oscillations by hypocapnia was studied in rat hippocampal slices. Field potential oscillations were induced by the cholinergic agonist carbachol under an N-methyl-D-aspartate (NMDA)-receptor blockade and were recorded in the dendritic layer of the CA3 region with parallel measurements of changes in interstitial and intraneuronal pH (pH_o and pH_i, respectively). Hypocapnia from 5 to 1% CO₂ led to a stable monophasic increase of 0.5 and 0.2 units in pH_o and pH_i, respectively. The mean oscillation frequency increased slightly but significantly from 32 to 34 Hz and the mean gamma-band amplitude (20 to 80 Hz) decreased by 20%. Hypocapnia induced a dramatic enhancement of the temporal stability of the oscillations, as was indicated by a two-fold increase in the exponential decay time constant fitted to the autocorrelogram. A rise in pH_i evoked by the weak base trimethylamine (TriMA) was associated with a slight increase in oscillation frequency (37 to 39 Hz) and a decrease in amplitude (30%). Temporal stability, on the other hand, was decreased by TriMA, which suggests that its enhancement in 1% CO₂ was related to the rise in pH_o. In 1% CO₂, the decay-time constant of the evoked monosynaptic pyramidal inhibitory postsynaptic current (IPSC) was unaltered but its amplitude was enhanced. This increase in IPSC amplitude seems to significantly contribute to the enhancement of temporal stability because the enhancement was almost fully reversed by a low concentration of bicuculline. These results suggest that changes in brain pCO₂ can have a strong influence on the temporal modulation of gamma rhythms.