Herein we report a patient with Behçet'slike syndrome, idiopathic CD4+T-lymphocytopenia, opportunistic infections, and a large polyclonal population of TCRαβ+CD4-CD8-T cells. Microfluorimetric analysis of peripheral blood mononuclear cells revealed CD4+T-cell counts of 10 ± 5/mm3. The CD3+T cells were 99% TCRαβ+, of which 74 ± 5% were CD4-CD8-. No clonal populations were detected by southern analysis for T-cell receptor Vβ gene rearrangements. No evidence of human immunodeficiency virus infection was present, although nocardia, candida, pneumocystis, cytomegalovirus, and herpes infections were documented. The concomitant presence of opportunistic infections and a large population of TCRαβ+CD4-CD8-T cells suggests a pathogenic association and an intense immune response to microbial lipid or lipoglycan antigens presented in the context of CD1 molecules. This case demonstrates the potential for idiopathic CD4+T-lymphocytopenia to occur in Behçet's-like syndrome with lethal consequences.