We have recently shown that CD30, a member of the tumor necrosis factor/nerve growth factor receptor superfamily, is preferentially expressed by human T cell clones producing T helper (Th) type 2 cytokines. We report here that costimulation with an agonistic anti-CD30 monoclonal antibody enhanced antigen (Ag)-induced proliferation and cytokine secretion by established human Th2 and Th0 clones. Moreover, costimulation of peripheral blood mononuclear cells with the same anti-CD30 monoclonal antibody resulted in the preferential development of Ag-specific T cell lines and clones showing a Th2-like profile of cytokine secretion. In contrast, early blockade in bulk culture of CD30 ligand-CD30 interaction shifted the development of Ag-specific T cells towards the opposite (Th1-like) phenotype. Taken together, these data suggest that CD30 triggering of activated Th cells by CD30 ligand-expressing Ag-presenting cells may represent an important costimulatory signaling for the development of Th2-type responses.