The development of T lymphocyte lines and clones of defined specificity has become an important method for investigating both T cell recognition of foreign antigens as well as T cell influence on B cells. In the present study, human antigen-specific T cell lines and clones have been derived from a patient with a naturally acquired filarial infection. These T cells are of the helper phenotype (Leu 1+, Leu 2-, Leu 3+) and are independent of exogenous interleukin-2. Furthermore, these T cells have been shown to require both antigen-presenting cells and antigen for optimal proliferation. Helper function mediated by these T cells as manifested by the in vitro induction of parasite-specific antibody was antigen-dose dependent, requiring much lower antigen concentrations than those necessary to induce blastogenesis. More importantly, there is an absolute requirement of the T cell line for HLA-DR histocompatible antigen-presenting cells; clones derived from this T cell line show a more specific DR-related restriction--to only one of the two parental DR haplotypes in antigen stimulated proliferative responses. Such parasite antigen specific human helper T cell lines and clones should prove useful in exploring the fine control of the host response to naturally acquired helminth infections. In addition, these long-term T cell lines and clones can provide a potent tool for examining not only the events involved in human T cell responses to parasite antigens, but also into the associated cellular and humoral factors necessary for the B cell responses which follow.