gamma/delta+ T-cells are a recently identified subpopulation of T-lymphocytes expressing an "alternative" T-cell receptor (TCR) molecule consisting of disulfate-linked or nonlinked gamma and delta chains. Despite a limited number of V gamma and V delta genes in the germ line, there is a large and diverse gamma delta TCR repertoire due to extensive N region variability. Recently developed monoclonal antibodies against V gamma and V delta gene products are useful reagents for the identification and isolation of gamma/delta+ T-cell subpopulations. The physiological significance of gamma/delta+ T-cells is still unknown. However, accumulating evidence indicates that human gamma/delta+ T-cells frequently recognize bacterial ligands as well as certain tumor cells. Interestingly, reactivity towards microbial antigens is usually restricted to a subpopulation of gamma/delta+ T-cells expressing a V gamma 9/V delta 2 TCR. However, different bacteria-reactive V gamma 9+/V delta 2+ gamma/delta+ T-cells display extensive N region variability, suggesting the involvement of a gamma/delta-specific superantigen in these responses. Little is known about the role of gamma/delta+ T-cells under pathological conditions. Rare cases of gamma/delta+ T-cell leukemias and lymphomas have been described. In addition, discrete changes in the distribution of gamma/delta+ T-cell subpopulations have been observed during HIV infection. Current thinking favors the interpretation that gamma/delta+ T-cells play a role in the immune reaction during infection and in the regulation of physiological or pathophysiological autoimmune responses.