Current views on the molecular mechanisms of the pH-dependence of gap junctions are mainly based on the experimental fact that extracellularly applied CO2 or other weak acids rapidly and reversibly block junctional conductance and also decrease intracellular pH. The data are presented suggesting that the mechanism of the uncoupling action of weak acids may not be restricted to the intracellular acidification. Hypotheses concerning possible protonation sites in the connexin molecules are also considered.