Effects of tricyclic antidepressants and MAO inhibitors on mitochondrial MAO activities in dog brain and liver with tyramine and serotonin as substrates and effects of oxygen in gas phase on these actions were studied. The pH optimum for tyramine oxidation was pH 8.0 and for serotonin oxidation was pH 8.8 in dog brain MAO activity. Tyramine and serotonin oxidation by dog brain MAO were inhibited by concentrations more than 10^-4 M of imipramine, desipramine, amitriptyline and nortriptyline, and pI₅₀ values with both substrates were 10^-3 M for these four antidepressants. The same results were obtained either 20% or 100% oxygen used as gas phase. Concentrations of 10^-8 M or more of tranylcypromine and pheniprazine inhibited brain MAO activity with both concentrations of oxygen and pI₅₀ values were approximately 5 × 10^-7 M in all cases. These inhibitory effects were 1, 000 times more potent than those of antidepressants. With 20% oxygen as gas phase, pI₅₀ values of the dog brain MAO by harmine were 10^-5 M for tyramine and 10^-7 M for serotonin oxidation, and with 100% oxygen as gas phase, they were 10^-4 M for tyramine and 10^-7 M for serotonin oxidation.<BR>Tyramine and serotonin oxidation by dog liver MAO were inhibited by concentrations more than 10^-4 M of imipramine, desipramine, amitriptyline and nortriptyline, and pI₅₀ values were 10^-3 M with both substrates for these four antidepressants. Concentrations of 10^-7 M or more of tranylcypromine and pheniprazine inhibited liver MAO activity with both substrates and with both concentrations of oxygen and pI₅₀ values were approximately 10^-6 M in all cases. With 20% oxygen as gas phase, pI₅₀ values of liver MAO by harmine were 2 × 10^-4 M for tyramine and 3 × 10^-6 M for serotonin oxidation, and with 100% oxygen as gas phase, they were 3 × 10^-4 M for tyramine and 5 × 10^-8 M for serotonin oxidation. Distinct differences of pI₅₀ values between tricyclic antidepressants and MAO inhibitors were observed, but correlation between MAO inhibitory effects and antidepressive effects was not found. It is suggesting that pharmacological effects of antidepressants are not caused only by inhibition of MAO activity in brain. From the result obtained the differences of inhibitory effects of harmine on oxygen consumption and of Km values when dog brain and liver MAO used as enzyme, it is also suggesting that there are multiple formes of MAO which shows different enzymatic characteristics in brain and liver.