1. The relationship between extracellular pH (pHe), intracellular pH (pHi) and lactate uptake was studied in the isolated perfused rat liver during simulated metabolic acidosis.
2. pHi fell to a considerably less extent than pHe when the latter was decreased from pH 7·4 to 6·7.
3. The liver took up lactate when pHi was greater than 7·0; at lower values of pHi lactate output occurred.
4. The relevance of these observations to the control of hepatic pHi and lactate metabolism is discussed.