The role of a parasite-produced or -induced soluble immunosuppressor in experimental kala azar was examined. It was found that in vivo infections with Leishmania donovani in the hamster (Mesocricetus auratus) produce a soluble immunosuppressor, which appears in the serum of the host and which reduces the proliferation of responding populations of murine splenocytes in a one-way mixed leukocyte reaction (MLR). The production in vitro infections of murine splenic macrophages from C57BL/6J ($Lsh sp{ rm s}$), C57L/J ($Lsh sp{ rm R}$) and BALB/c strains, the suppressive activity was not contained in either parasite-conditioned culture medium or in parasite extracts or from macrophages which have internalized killed parasites or inert particles and it is not blocked by the action of 2-mercaptoethanol or indomethacin in the culture medium. The suppressor was found to be able to selectively inhibit or reduce the proliferation of splenocytes of both the C57BL/6J and C57LN strains in a one way MLR, with the level of suppression being significantly greater upon splenocytes of the susceptible $Lsh sp{ rm s}$ strain. The suppression was dependent upon the genotype of the macrophages present in the responding population. The suppressor was also able to significantly inhibit the processing of human serum albumin by macrophages, to reduce the number of Ia ligands on the surfaces of macrophages and the production by these cells of IL-1 upon silica stimulation. / Significant reduction was also seen in the production of IL2 and in the expression of its receptor by PHA-stimulated T cells exposed to the suppressor. Partial purification and identification of the suppressor demonstrated that the suppressive activity was present in fractions between 30 and 50 kDa in size; the suppressor was also heat labile and freeze-thaw sensitive. The suppressive molecule(s) may therefore play a significant role in the establishment and pathology of L. donovani infections.

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