Mice were injected via tail vein with emulsions of fluorocarbon (FC), an oxygen-carrying compound that has great potential as a blood substitute. Different types of FCs were used. All produced vacuolar changes in hepatocytes, and in reticuloendothelial cells throughout the body. In the liver, occasional inflammatory foci were also observed, but fibrosis was never seen. The vacuolated cells, presumably containing FC, were found as late as 1 yr following a single infusion. However, such cells might also disappear from the liver and spleen. The numbers of affected cells and their rate of disappearance depended on the type of FC, the amount of FC infused and the length of time between infusion and killing. Fluorodecalins, especially PP-5 (C10F18), produced the least amount of change and the most readily reversible change of all FCs tested. The morphologic observations suggest that PP-5 would be more suitable as a blood substitute than the other FCs tested. However, other studies have shown that apparently healthy long-term survival is obtainable even when the infused FC is one that produces extreme vacuolar change in the liver and spleen.