Common variable immunodeficiencies (CVID) are a heterogeneous group of antibody deficiency disorders complicated by autoimmune, lymphoproliferative and/or granulomatous manifestations, suggesting variations in immunoregulation. We sought to quantify regulatory CD4 T cells (T(reg) cells) in the blood of CVID patients and to correlate the frequency with clinical manifestations and classification subgroups. Blood samples from 99 CVID patients in Freiburg, London and Sydney, who had been phenotyped clinically and stratified according to their memory B cell phenotype (Freiburg and Paris classification schemes), were analysed for the proportion of T(reg) cells, defined either as CD25(+)/forkhead box P3 (FoxP3)(+), CD25(+)/CD127(low)/FoxP3(+) or CD25(+)/CD127(low) CD4(+) T cells, and results compared with 49 healthy controls. Irrespective of the phenotype used to define them, there was a significant decrease in the T(reg) cell proportion in patients with granulomatous disease and immune cytopenias. This allowed the definition of a subgroup of CVID patients with abnormally low T(reg) cells, which had a higher rate of these two manifestations as well as autoimmune disease in general. There was also a significant reduction in the proportion of T(reg) cells in the Freiburg group Ia compared with other CVID patients and controls, but there were no differences between the Paris groups. The reduction in T(reg) cells in subsets of CVID patients may be relevant to their clinical manifestations, and may contribute to our understanding of the pathogenesis of CVID complications.