A study was made of the humoral immune response of BALB/c mice to various doses of artificial proteins that contained biologically active fragments of human interferon alpha 2 (IFN-alpha 2) and insulin. The insulin fragment had no effect on the response to any protein construct. The IFN-alpha 2 fragment increased the titer of antibodies against the construct. Mapping of continuous B epitopes with immune sera revealed several antigenic determinants, the C end of the IFN-alpha 2 fragment with the adjacent de novo protein region being immunodominant. More effective binding of serum antibodies with the constructs containing the IFN-alpha 2 fragment was attributed to antibody interaction with the fragment and to a better recognition of the entire protein construct by the immune system.