The effects of serum protein concentration (SPC) on serum protein/gas partition coefficient and of hematocrit ratio (HT) on red cell/gas partition coefficient during halothane, enflurane or isoflurane anesthesia were examined in dogs. Furthermore, their effects on Minimum Alveolar Concentration (MAC) of the three anesthetics were also studied. Serum protein/gas partition coefficient and red cell/gas partition coefficient were significantly changed by the alteration of SPC and HT, respectively, in vitro. Concentrations of these anesthetics in blood at 1 MAC were only related to SPC in vivo. This suggeste that the solubility of inhalation anesthetics may be influenced by the composition of red cells and serum protein. In vivo, as SPC increased, MAC of these anesthetics increased linearly (p<0.01). MAC of enflurane was affected most by SPC and followed by that of isoflurane. MAC of halothane and enflurane was not affected by HT, but that of isoflurane increased linearly (p<0.01) as the HT increased. This suggested that the protein concentration difference between brain tissue and serum alters the action of the anesthetics and that HT alone alters the action of isoflurane only.