Cryostat sections from 10 patients with localized cutaneous leishmaniasis (LCL) and eight patients with diffuse cutaneous leishmaniasis (DCL) from Ethiopia were studied with immunofluorescence methods for the phenotypic characterization of cells in the lesions. Higher numbers of Leu 2+ and Leu 3+ cells (P less than 0.005) were found in LCL than in DCL, while the Leu 3a + b/Leu 2a ratios were the same. No differences were found in the numbers of transferrin receptor, HLA-DR, and HLA-DQ expressing cells in the granulomas. Significantly (P less than 0.0001) lower numbers of IL-2 receptors expressing (Tac+) cells were found in DCL than LCL lesions, suggesting interference in the activation of the T cells. IL-2-containing cells were absent in DCL and were found in LCL lesions. Epidermal keratinocytes above the LCL but not the DCL lesions expressed HLA-DR (but not HLA-DQ) antigen, suggesting a lower gamma-interferon production in the DCL granulomas. The number of Langerhans' cells (Leu 6+) was higher in the epidermis of DCL (P less than 0.005) than in LCL, while a lower number of Leu 6+ cells were seen in the dermal lesions (P less than 0.001). These observations could account for some of the mechanisms responsible for the disturbed immunostimulation and immunoregulation observed in the lesions of DCL.