Previous studies have demonstrated that dye coupling between neurons can be reduced by maneuvers that reduce intracellular pH. However, it is apparent that marked extracellular alkaline- as well as acid-going pH shifts can occur in the mammalian CNS. In light of the fact that an applied change in extracellular pH may produce a damped change in intracellular pH in the same direction, in this study we have examined the effects of exposure to high extracellular pH (achieved by raising [HCO3-] at a constant PCO2) on the incidence of Lucifer yellow dye coupling between CA1 pyramidal neurons in the rat hippocampal slice. Under standard conditions (pH 7.4), 44% of CA1 pyramidal neurons were dye-coupled, and the mean number of neurons stained per injection was 1.62. A marked increase in the incidence (88%) and extent (mean number of neurons stained per injection, 3.25) of dye coupling was observed during exposure to high-pH medium (pH 7.9). Under both standard and high-pH conditions, dye coupling was associated with the ability of CA1 pyramidal neurons to generate bursts of action potentials in response to intracellularly applied depolarizing current pulses. The results provide additional evidence that dye coupling between hippocampal pyramidal neurons may be modulated dynamically and may have implications for the genesis of synchronized epileptiform activity under alkalotic conditions.