BALB/c mice develop fatal illness following infection with Leishmania major despite expansion of helper L3T4+ T cells in the draining lymph nodes and spleen. Healer mice, either genetically resistant C57BL/6 or BALB/c that have been pretreated with monoclonal antibody GK 1.5, also develop expanded numbers of L3T4+ T cells at the time of healing. Lymph node cells from healer mice produce gamma-interferon in vitro and message for gamma-interferon can be recovered from the lymph nodes during healing in vivo. Conversely, cells harvested from non-healer mice during the course of infection produce minimal gamma-interferon in vitro and have little message for gamma-interferon detectable in vivo. When the same Northern blots are hybridized for IL-4, large amounts of IL-4 message are detected only in cells from non-healer mice. The data are consistent with the expansion of type 1 helper cells (Th1) during healing and type 2 helper cells (Th2) during progressive leishmania infection.