Since morphine has been shown to inhibit potassium-stimulated oxygen uptake of rat brain slices incubated in calcium-free Ringer’s solution experiments were done to clarify this finding. We found that altering conditions to favor morphine uptake resulted in inhibition of stimulated oxygen uptake by morphine when the slices were incubated in conventional Ringer’s solution. These alterations consisted of (a) incubation of slices in 0.01 M morphine, (b) incubation of slices in 0.01 M KC1, or (c) pretreatment with 100 mg/kg morphine 30 min prior to sacrifice. The data suggest that permeability of the cell membrane is an important factor in the effect of morphine on the oxygen uptake of rat brain slices.