Because of the high conservativity of cytochrome b5 cytosolic domain (t-cytochrome b5) among mammalian species the antibodies against bovine t-cytochrome b5 were successfully obtained only from evolutionary distant species, (chicken). Antigenic mapping of t-cytochrome b5 by the peptide scanning method showed the presence of a large set of linear B-epitopes of this protein.This well consistent with high content of water-accessible amino acid residues and polypeptide chain turns in its molecule. Linear B-epitopes of t-cytochrome b5 are presumably located in sites with species specificity of the amino acid sequence, despite of the high-degree surface exposure of the highly conservative site, which is probably responsible for the interaction with cytochrome P450. It can be explained by the absence of the effective T-helper support of the antibody response to amino acid sequence sites that are identical to self proteins of an organism. Nevertheless, antibodies against bovine t-cytochrome b5 possess high cross-reactivity with regard to rabbit full-sizea cytochrome b5 because of the presence of one identical linear B-epitope and cross-interactions between other antigenic sites with minor structural differences.