Septic shock was induced in adult baboons by the infusion of liveEscherichia coli. A progressive derangement in skeletal muscle cell function was documented by the direct measurement of declining transmembrane potential difference (PD). A concurrent depolarization of the red blood cell (RBC) was characterized by cellular uptake of chloride, sodium, and water, and loss of potassium. The decrease in RBC PD was significantly greater than the change predicted to occur from acidosis alone. These findings are compatible with changes in membrane permeability and decreased active transport. The continuous accumulation of RBC adenosine triphosphate during shock suggests decreased energy utilization rather than decreased energy production as a factor leading to diminished active ion transport.