Anaphylactic histamine release from minced guinea pig lung, suspended in a substrate-free medium, was completely inhibited by lack of oxygen but was unaffected by low oxygen tension reducing the oxygen uptake up to one-third of its normal value. Glucose, pyruvate, α-ketoglutarate, and fumarate did not influence histamine release, while succinate in a relatively low concentration had a stimulant effect; the succinate-induced stimulation appeared to be related to its oxidation in Krebs cycle. Malonate, 40 mm, almost completely blocked anaphylactic histamine release but the inhibition was noncompetitive and could not be reversed by succinate. Fluoroacetate, 50–100 µm, and arsenite, 5–10 µm, caused about 50% inhibition of histamine release, probably by blocking the oxidation of citrate and α-keto acids, respectively. Inhibition with both the agents could be reversed by succinate.