Effects of monoamine oxidase (MAO) inhibitors on two kinds of membranes, biological and model membranes, were studied Erythrocytes and freshly isolated hepatocytes from rats were used to examine the effects of MAO inhibitors on biological membranes. Hydrazide and hydrazine derivatives, except isonicotinic acid, enhanced hemolysis and the stability of isolated hepatocytes membrane. Deprenyl and moclobemide stabilized the biological membranes of erythrocytes and isolated hepatocytes, and moclobemide induced slight enzyme leakage from isolated hepatocytes. Clorgyline and brof aromine had opposite effects. At lower concentrations, they remarkably inhibited hemolysis and enzyme leakage. At higher concentrations, they enhanced hemolysis and apparent enzyme leakage. To investigate effects of MAO inhibitors on a model membrane, changes of phase transition temperature of dipalmitoyl phosphatidylcholine liposomes was determined. Brofaromine induced the most extreme decline of phase transition temperature. Deprenyl and clorgyline also induced moderate decline of transition temperature, and phenylhydrazine and ρ-tolylhydrazine induced mild decline. These results suggest that the effects of clorgyline and brofaromine on the membranes of erythrocytes and freshly isolated hepatocytes might be partly due to increased fluidity of membrane phospholipid. These severe membrane effects of MAO inhibitors might be the reason for their cytotoxicity.