Blood-brain barrier permeability to L-lactate was studied in 18 patients with the double indicator technique. Venous outflow curves were obtained during normo- and hypercapnia and were analyzed by means of a model that takes tracer backflux and capillary heterogeneity of transit times into account. The average unidirectional extraction of L-lactate was 15%; the transport from the blood to the brain (PS1) was 0.081 ml g-1 min-1 and the transport from the brain to the blood (PS2) was on the same order of magnitude. In hypercapnia, arterial pH decreased from 7.39 to 7.26 and PS1 to L-lactate increased significantly by 110%. PS2 also increased although a statistically significant difference compared to the resting state was not reached. It is concluded that L-lactate is easily taken up by the human brain, and that the mechanism by which it crosses the blood-brain barrier is equilibrative. Furthermore, the brain permeability to lactate is enhanced by hypercapnia and the mechanism is believed to act through the decrease in pH.