Δ 1-Tetrahydrocannabinol affects the configurational integrity of rat liver mitochondria to a degree dependent upon its concentration. When Δ 1-tetrahydrocannabinol concentration is increased, the mitochondria pass through three different morphological stages, which are visualized by electron microscopy. These stages are correlated with changes in oxygen uptake, ATPase activity and turbidity. Starting with control mitochondria, designated as Stage A, addition of 15 μg Δ 1-tetrahydrocannabinol per mg protein results in maximum stimulation of oxygen uptake (Stage B). In the presence of 50 μg Δ 1-tetrahydrocannabinol per mg protein this stimulation vanishes, the inner mitochondrial structure is disrupted and maximum values of swelling and ATPase activity are attained (Stage C). At higher Δ 1-tetrahydrocannabinol concentrations, up to more than 100 μg per mg protein, both stimulation of ATPase activity and swelling diminish. These effects are proposed to be associated with bonding of the hydrophobic Δ 1-tetrahydrocannabinol to some protein-phospholipid receptors in the mitochondrial membrane.