Onchocerciasis is a chronic infectious disease caused by the filarial nematode Onchocerca volvulus. A minor population of human gammadelta T cells expressing Vdelta1 chains is preferentially stimulated by O. volvulus ligands in vitro. Therefore, the nature of the parasite ligand and the effector functions of Vdelta1+ T cells stimulated by O. volvulus was investigated. A 5- to 30-kDa ligand from the adult parasite lysate that is sensitive to proteinase treatment was identified. Presentation for preferential stimulation of Vdelta1+ T cells required processing. After in vitro stimulation with O. volvulus in the presence of interleukin-2, Vdelta1+ T cells produced interferon-gamma but not interleukin-4 and exhibited NK cytolytic activities. It is concluded that somatic 5- to 30-kDa protein ligands from O. volvulus stimulate Vdelta1+ T cells and that Vdelta1+ T cells play a role in immunity to O. volvulus.