Kenyan subjects with visceral leishmaniasis were examined for evidence of increased production of soluble interleukin-4 receptor (sIL-4R). Soluble IL-4R regulates the bioactivity of IL-4, a cytokine important in mediating progressive forms of leishmaniasis. Persons with visceral leishmaniasis sustained 8- to 10-fold more circulating sIL-4R compared with Papua New Guinea residents with documented filariasis or uninfected Kenyan and North American subjects. Soluble IL-2R concentrations were elevated nonspecifically in both visceral leishmaniasis and filariasis patients. These findings are significant given that IL-4 induces sIL-4R in mice, and treatment with recombinant sIL-4R cures progressive murine leishmaniasis dependent on IL-4 bioactivity. Further studies are indicated to determine whether the immunologic detection of IL-4 produced in human visceral leishmaniasis is obscured because of sequestration by soluble receptor and whether the production of sIL-4R is relevant to the pathogenesis of visceral leishmaniasis.