Leishmania aethiopica infection results in two main clinical entities, diffuse disease (DCL) and localized ulcers (LCL). The lack of reactivity to leishmanial antigens has been attributed, among other things, to some inherent immunological defect of the host or considered as a consequence of the initial site of infection. Properties unique to the infecting parasite have been said to contribute little if anything to the differences between DCL and LCL found in the same areas of Ethiopia. Data are given to show that infected individuals respond by higher production of IL-2 to antigens from LCL isolates (lcl antigen), than to antigens derived from DCL isolates (dcl antigen). Furthermore, dcl antigen induced less gamma interferon from lymphocytes of all individuals tested than did lcl antigen. Lymphocytic proliferation of cells from control individuals working in the endemic area was higher in response to lcl isolates than to dcl isolates. These findings suggest that some differences in the parasites may contribute to the clinical outcome of infection with L. aethiopica.