In mice, infection with Leishmania by the subcutaneous route becomes evident after about 2 months. This delay impedes the selection of monoclonal antibodies able to interfere with the infectiousness of the parasite. Using an in vivo culture system--intraperitoneal injection of TG 180 sarcoma cells along with promastigotes or amastigotes--it was possible to define within 15 to 20 days a monoclonal antibody preventing the development of Leishmania. Pretreatment of promastigotes and amastigotes of several Leishmania species with a monoclonal antibody raised against Leishmania infantum prevented infection equally in either system. These cross-reactions may be of importance in designing new approaches of immunotherapy.