In normal persons, circulating gammadelta T cells comprise a minor cell subset (0.5%-6% of total lymphocytes). gammadelta T cells were studied in the context of therapeutic immunosuppression in transplanted patients. Flow cytometry detected an expansion of gammadelta 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 gammadelta T cells in allograft recipients. Multivariate analysis further indicated that CMV infection was the only independent parameter associated with >6% gammadelta T cells. gammadelta T cell expansion directly followed CMV infection and was never observed in persons who did not develop CMV infection. Thus gammadelta T cells may represent a first-line defense mechanism against CMV infection in a person whose alphabeta T cell response has been weakened by immunosuppression.