We have recently reported that a unique antigenic structure, designated as Common epitope 1, was found to be shared by human recombinant IFN alpha-2 and the human fibroblast IFN beta. The Common epitope 1 was identified with the aid of a synthetic IFN alpha-2 fragment SH 132-137. Based on this observation, we proposed the hypothesis that an antigenic relationship should exist also between natural human leukocyte IFN alpha and natural human fibroblast IFN beta. However, we were not able to detect any Common epitope 1 in preparations of conventional human leukocyte IFN alpha. In the present study, we were looking for a possible explanation of absence of the Common epitope 1 in conventional leukocyte IFN alpha. First, we demonstrated its acid labile nature in the recombinant IFN alpha-2 molecule and second, we proposed that the pH 2 lability of this unique epitope might be responsible for the lack of antigenicity also in pH 2-treated (conventional) leukocyte IFN alpha preparations. Actually, when pH 2 non-treated leukocyte IFN alpha was examined, we succeeded in demonstration of the Common epitope 1 in IFN-preparation. Moreover, anti-serum against pH 2 non-treated IFN alpha was capable of neutralizing both the conventional i.e. pH 2-treated leukocyte IFN alpha and fibroblast IFN beta. It is concluded that the nomenclature distinguishing two classes (i.e. alpha and beta as class I and gamma as class II) of IFNs is more appropriate than the current official nomenclature distinguishing three antigenic classes of IFNs.