In a prospective study we investigated the association of kidney graft rejection with pre- and posttransplant B cell responses in vitro after stimulation with pokeweed mitogen, Staphylococcus aureus Cowan I (SAC I), or donor lymphocytes. B cell differentiation was assessed in a reverse hemolytic plaque assay. Elevated pretransplant PWM- or SAC I-stimulated B cell responses were found to define patients with a high incidence of rejection episodes in the first 30 days posttransplant (P less than 0.005 and P less than 0.05, respectively). Elevated pretransplant donor cell-stimulated B cell responses were associated with a high risk of irreversible rejection (P less than 0.005). A posttransplant rise in donor cell-stimulated B cell responses was associated with an increase risk of a subsequent rejection crisis (P less than 0.05). Our data suggest that patients at risk of early rejection may identified by pretransplant testing of B cell responses.