Individuals with visceral leishmaniasis, or kala azar (KA) and individuals with post-KA dermal leishmaniasis (PKDL) are considered to be reservoirs of transmission of Leishmania donovani in India. When intracellular amastigotes were used to assess the natural susceptibility that PKDL isolates and KA isolates have to sodium antimony gluconate (SAG), the mean ED(50) was found to be 12.0+/-2.49 and 11.0+/-1.38 microg/mL, respectively; and there was a significant correlation with the clinical response (r rank=0.99). All KA isolates, as well as a significant proportion (55%) of PKDL isolates from high-endemicity zones, were resistant to SAG. The median ED(50) for SAG-resistant PKDL isolates (20.0 microg/mL) was significantly higher (P<.05) than that for SAG-resistant KA isolates (15.7 microg/mL). SAG-resistant PKDL isolates may contribute to KA's increased refractoriness to SAG, via anthroponotic transmission of SAG-resistant strains.