While characterizing the functional properties of T -cells across the leprosyrnspectrum, significant differences between proliferation ofT-cells isolated from bloodrnand tissue lesions were consistently noted. The differences occurred in more thanrn80% of cases when comparison was made between blood and skin derivedrnlymphocytes from leprosy patients; in 50-80% cases when comparing lymphocytesrnisolated from nerves with those from blood of leprosy patients, and > 85 % whenrncomparing lymphocytes derived from blood or skin lesions of patients with otherrnskin inflammatory diseases. The differences were seen throughout the leprosyrnspectrum. Skin derived lymphocytes from patients with multibacillary (ME) orrnpaucibacillary (PB) leprosy proliferated poorly when compared to lymphocytesrnisolated from blood and lymphocytes derived from nerves of some PB and mostrnMB patients proliferated poorly when compared to lymphocytes from blood.rnStimulation with a strong co-mitogen did not restore responsiveness of T -cellsrnisolated from skin lesions. Cells from different tissues also differed from each otherrnin activation requirements. Analysis of molecules known to differ between T-cellrnsubpopulations and to playa role in T -cell activation indicated some differences inrnthe molecules expressed between blood and tissue lesion derived T-cells. However,rnthe differences observed did not appear to be striking enough to account for the poorrnresponsiveness of tissue lesion derived T-cells. Assays for lymphokine productionrnshowed that more IL-2 and IL-4 were produced by T-cell cultured from bloodrncompared to cells from skin, IFN-/, production was found to be made in equalrnamount by cells from both tissues, The absence of marked differences between blood and lesion derived T-cells, except ill the production of IL-2 and IL-4,rnindicates that a possible explanation for the difference in proliferation is anergy asrnanergic cells are not able to produce IL-2 or respond to IL-2 from an externalrnsource. Other possibilities which may contribute to the difference are discussed