The effects of pyrocatechol and its monosubstituents on the hemolysis of bovine erythrocytes induced by the hydrophilic free radical initiator, 2,2'-azobis(2-amidinopropane)dihydrochloride (AAPH), were investigated. Relatively hydrophilic derivatives such as the 4-COO- substituent (protocatechuic acid), which are almost completely ionized at physiological pH, have a more inhibitory effect than the more hydrophobic derivatives such as the 4-C(CH3)3 substituent. In the presence of relatively low concentrations of the latter derivatives, the onset of hemolysis was retarded, but the hemolysis then proceeded more rapidly and the time, at which almost complete hemolysis occurred, was almost the same as that in their absence. Regression analysis on the relationships between the inhibitory effects of the derivatives and their redox potentials and hydrophobic parameters revealed that the inhibitory activity of the catechol derivatives on AAPH-induced hemolysis was controlled by low hydrophobicity as well as electron donor activity. In the presence of relatively hydrophobic catechol derivatives, oxidation of hemoglobin was observed. These findings suggest that interaction of these derivatives with hemoglobin after their penetration erythrocytes reduced the scavenging activity against free radicals. Their interaction with membrane or cytoplasmic components may cause the increased hemolysis rate after the onset of hemolysis at relatively low concentrations.