Multiple-indicator dilution experiments with labeled lactate were performed in the livers of anesthetized dogs. A mixture of ⁵¹Cr-labeled erythrocytes, [³H]sucrose, and L-[1-¹⁴C]lactate or a mixture of ⁵¹Cr-labeled erythrocytes, [¹⁴C]sucrose, and L-[2-³H]lactate was injected into the portal vein, and samples were obtained from the hepatic vein. Data were evaluated using a model comprising flow along sinusoids, exchange of lactate between plasma and erythrocytes and between plasma and hepatocytes, and, in the case of L-[1-¹⁴C]lactate, metabolism to H[¹⁴C]O₃ within hepatocytes. The coefficient for lactate efflux from erythrocytes was 0.62 ± 0.24 s¹, and those for influx into and efflux from hepatocytes were 0.44 ± 0.13 and 0.14 ± 0.07 s¹, respectively. The influx permeability-surface area product of the hepatocyte membrane for lactate (P_inS, in ml · s¹ · g¹) varied with total flow rate (F, in ml s¹ · g¹) according to P_inS = (3.1 ± 0.5)F + (0.021 ± 0.014). Lactate in plasma, erythrocytes, and hepatocytes was close to equilibrium, whereas lactate metabolism was rate limiting.