Forty-two of 81 dogs from a family of Japanese Shiba dogs had red blood cells with a high K and a low Na concentration (HK). Of the HK dogs, 32 were high K and low glutathione (HK/LG) and 10 were high K and high glutathione (HK/HG). These variants were found in both males and females. The phenotype of HK was inherited in a recessive mode as reported earlier. A high incidence of HK/LG dogs was found in this family, and the phenotype was also inherited in a recessive mode. Glutamate (Glu) influx, which defines the cellular glutathione concentration, was lower in HK/LG cells than in HK/HG cells (in some cases extremely low). The fact that the red blood cells of HK/LG dogs have the two varying characteristics of a remaining Na, K-pump and low Glu transport suggests that 2 or more genes may be involved. Since an extremely low Glu influx was also found in normal low K and high Na (LK) red blood cells, the characteristic of low Glu transport also exists in LK cells. The phenotype of low Glu transport may also be inherited in a recessive mode. This family therefore had a very high incidence of homozygous recessive genes which control the phenotypes for the Na, K-pump and low Glu transport.