In normal persons, circulating γδ T cells comprise a minor cell subset (0.5%–6% of total lymphocytes). γδ T cells were studied in the context of therapeutic immunosuppression in transplanted patients. Flow cytometry detected an expansion of γδ T cells in 31 of 205 renal allograft recipients and in 2 of 41 uremic patients but in none of 45 healthy subjects. Univariate statistical analysis identified cytomegalovirus (CMV) infection (P < .001), second graft (P < .001), and antithymocyte globulin treatment (P = .01) as three variables associated with high levels (⩾6%) of circulating γδ T cells in allograft recipients. Multivariate analysis further indicated that CMV infection was the only independent parameter associated with > 6% γδ T cells. γδ T cell expansion directly followed CMV infection and was never observed in persons who did not develop CMV infection. Thus γδ T cells may represent a first-line defense mechanism against CMV infection in a person whose αβ T cell response has been weakened by immunosuppression.