Cytokine mRNA levels were measured in serial splenic aspirates from 27 patients with visceral leishmaniasis during monotherapy with interferon-γ (IFN-γ; n = 9), sodium antimony gluconate (SAG; n = 8), or amphotericin B lipid complex (ABLC; n = 10). At baseline, mRNA for IFN-γ was detected in 18 (86%) of 21 patients, and mRNA for interleukin (IL)-10 and IL-4 was detected in 21 (100%) and 10 (48%) of 21 patients, respectively. With IFN-γ treatment alone, levels of IFN-γ mRNA decreased by day 10 and then returned to baseline levels; IL-10 mRNA levels were high throughout treatment. In the SAG and ABLC groups, levels of IFN-γ and IL-10 mRNA decreased significantly. Polarized Th2 cell type responses do not appear to develop in Indian kala-azar; instead, there is an initial mixed Thl-Th2 cell picture. With successful treatment and resolution of infection, both components of the immune response appear to involute.