Recombinant human (r)IFN-alpha 2 is successfully used in treatment of haematopoietic malignancies, lymphomas and viral hepatitis B and C as well. One of undesired side-effects of rIFN-alpha 2 is its immunogenicity which could decrease therapeutic potential of the drug. Formation of antibodies against rIFN-alpha 2 in man represents a complex process, in which many mutually interacting variables are involved. Factors influencing the humoral response against the recombinant homologue of human IFN-alpha 2 have not been unambiguously determined yet. In general, two categories of these factors--exogenous and endogenous (physiological)--are considered. The exogenous factors determine structural differences of the recombinant protein from the native IFN-alpha 2. Their influence on the formation of therapy-induced antibodies could be limited by the selection of suitable rIFN-alpha 2 subvariant, suitable storage of the preparation and by treatment regimen. On the other side, current knowledge of the endogenous factors, which function at the level of patient's organism, do not allow to propose efficient ways of their elimination. (Tab. 2, Ref. 28.)