1. Mean intracellular pH (pHi) and lactate have been measured simultaneously in the isolated perfused rat liver on two successive occasions separated by an interval of 20 min. In some experiments extra lactate was added to the perfusion medium immediately after the first measurement of pHi.
2. There was a direct relationship between the change in pHi over this interval and the simultaneous change of lactate uptake.
3. This finding is consistent with the hypothesis that lactate enters the liver cell at least partly in the ionized form and that its metabolism is accompanied by the effective production of hydroxyl ions.
4. These observations are discussed in terms of a possible control mechanism for lactate uptake by the liver.