Breath-by-breath gas exchange was studied in 10 subjects during and after transitions between dry conditions and head-out immersion in thermoneutral conditions. Cardiac index (CI) was estimated by means of impedance cardiography. Previous largely qualitative models of changes in tissue gas stores after blood volume shifts could be confirmed and extended to include a quantitative analysis of O2 and CO2 tissue stores. An increase in CI by 47.0% during immersion was associated with an increase in the tissue O2 stores by 122 ml/m2 and a decrease in the tissue CO2 stores by 148 ml/m2. The time constants for the recovery of O2 uptake (tau O2) and CO2 elimination after initial increases after the dry-to-immersion transition were 32.4 and 79.3 s, respectively. The decrease in CI on return to the dry conditions was associated with a drop in tissue O2 stores and a tau O2 of 144 s. The increase in tissue O2 stores during immersion as well as the difference in tau O2 between the two transitions were larger than could be explained by the change in CI only. This was attributed to changes in the distributions of peripheral blood flow and venous blood volume. Compared with the O2 stores, the decrease in CO2 stores was better predicted by the change in CI. The present results emphasize that the changes in pulmonary and tissue gas exchange imposed by head-out immersion transients mainly reflect movement of gas in and out of body stores.