Resistance to the Leishmaniae is associated with interferon (IFN)-gamma mediated activation of macrophages. In this study, Balb/c mice were infected with three Leishmania strains that cause progressively growing cutaneous lesions without obvious dissemination: L. mexicana mexicana giving rise to rapidly growing lesions, and L. (Viannia) panamensis and L. mexicana-like, which both cause slowly developing lesions. The rate of lesion growth was compared to induction of early local and systemic IFN-gamma responses. All the three parasite strains induced increased levels of IFN-gamma transcripts 24 h after infection. Infection with the more aggressive strain resulted in a notably lower IFN-gamma response when compared to infection with the two low pathogenic strains. Interleukin-4 (IL-4) mRNA appeared 7 days after infection with L. (Viannia) panamensis and L. mexicana-like but not with L. mexicana mexicana. Thus, virulence of these Leishmania strains could not be associated with induction of IL-4 during the first week after infection. In addition, none of the Leishmania strains induced detectable mRNA for IL-12 or inducible nitric oxide synthase (iNOS). These data present a picture somewhat different from that which has been described in L. major experimental infection.