In this study, we measured gamma interferon production in mononuclear cell cultures from patients with diverse forms of leprosy and American cutaneous leishmaniasis. We studied patients with lepromatous, borderline lepromatous, borderline, and borderline tuberculoid forms of leprosy, as well as a Mitsuda-negative contact. In leishmaniasis we studied patients with localized cutaneous, mucocutaneous, and diffuse cutaneous forms of the disease. High correlation was observed between gamma interferon production and lymphocyte proliferation assays in both diseases. Resistant forms of both diseases showed significant reactivity, while the severe progressive forms were characterized by insignificant responses in both assays. Localized cutaneous leishmaniasis is characterized by variability in gamma interferon production, which may be of prognostic value in longitudinal studies.