T-helper cells play a central role in the onset and regulation of the antigen-specific immune response. In swine, two subpopulations of CD4 positive T-helper cells could be defined in extra-thymic compartments. Both differ in the surface antigen expression of distinct antigens. Besides the CD4(+)CD8(-) T-helper cell subpopulation representing the phenotype of T-helper cells known from other species, in swine CD4(+) T-helper cells exist showing expression of CD8alpha and MHCII molecules.In primary in vitro immune reactions after simulation with SEB the main response is distributed to the CD4(+)CD8(-) T-cell subpopulation, which contains the majority of naive T-helper cells. During the immune response CD8alpha as well as MHCII molecules are expressed on the surface of activated T-helper cells. This in vitro maturation is combined with a down-regulation of CD45RC. Thus, activated T-helper cells represent a cell phenotype with high similarity to the second porcine T-helper cell subpopulation. This CD4(+)CD8alpha(+) subpopulation contains in its majority MHCII(+) and CD45RC(-) cells. In a secondary in vitro immune response against classical swine fever virus only the CD4(+)CD8(+) T-helper subpopulation is able to respond. Therefore, T-helper memory cells can be distributed to this T-lymphocyte subpopulation. In summary, naive CD4(+)CD8(-)MHCII(-) porcine T-helper cells show an extra-thymic maturation to committed CD4(+)CD8alpha(+)MHCII(+) T-helper cells.