BALB/c mice differ from CBA/H, (CBA/H x BALB/c)F1 and C57BL/6 mice in being highly susceptible to infection with a particular isolate of the intramacrophage protozoan parasite, Leishmania tropica. This is true over a wide range of challenge doses of promastigotes administered intradermally although, at low doses, male BALB/c are able to restrict the rate at which cutaneous lesions increase in size. Resistance to infection in highly susceptible hypothymic nude (nu/nu) mice of CBA/H and C57BL/6 genotypes can be achieved readily with as few as 10(6) syngeneic lymphoid cells. In CBA/H.nu/nu mice, Lyl+2- cells in low dose cellular inocula appear to be involved in restoring resistance (i.e. rapid resolution of infection). Surprisingly, a proportion of BALB/c.nu/nu mice injected with syngeneic lymphoid cells are resistant and thus differ from intact BALB/c mice or non-reconstituted BALB/c.nu/nu mice. In keeping with a high efficacy of limited numbers of T cells following minimal reconstitution, the majority of nude mice implanted subcutaneously with allogeneic, irradiated, neonatal thymus grafts are resistant to L. tropica infection. Genetic features of the nude mouse, such as defect in skin, may contribute to the extraordinary potency of T cell reconstitutive manipulations. Evidence was obtained that BALB/c.nu/nu skin on BALB/c.nu/+ recipients did not support the development of lesions as readily as normal skin sites.