It is widely accepted that transfusions are beneficial to the outcome of renal allotransplantation. Whereas some investigators suggested that transfusions may induce both specific and nonspecific suppression of the cell-mediated immune response, others disagree. To lend clarity to this discrepancy, we collected 40 serum samples before and after blood transfusion therapy of first-time cadaveric renal allograft recipients and evaluated each for T cell and B cell cytotoxic antibodies using an Amos modified complement-dependent microlymphocytotoxicity assay. When greater than 10% of the panel cells reacted with a grade 4 or better, the panel was considered significant, and when a lymphocyte specificity was lysed by antibody-rich serum greater than 50% of the time, the antibody was considered specific. Control T and B cell PRA assays employed sera from 27 normal nontransfused volunteers of similar age and sex. Survival distributions of differences in the PRA before and after blood transfusions and posttransfusion PRA levels were compared using the Gehan generalized Wilcoxon test. Other factors which influence allograft survival such as HLA-A, -B and -DR matches, number of blood transfusions, immunosuppressive therapy, age, sex, parity, previous positive crossmatch, circulating cytotoxic antibodies matching the graft, prior dialysis, length of time on the waiting list, lapse of time between transfusion and transplantation and the underlying primary diagnosis were also considered using the Gehan generalized Wilcoxon test or the chi 2 approximation. Transfusion-related B cell cytotoxic antibodies, HLA-DR monospecific or multispecific antibodies and HLA-A, -B matching extended graft survival in a significant manner. Sex influenced the production of B and T cell transfusion-related cytotoxic antibodies with females producing greater quantities of antibodies than males. Parity and the production of monospecific or multispecific antibody were associated with an increase in transfusion-related B cell cytotoxic antibody. A difference in sex was not linked to the production of monospecific or multispecific HLA-DR antibodies. The majority of males failed to respond to multiple blood transfusions with the production of B cell cytotoxic antibodies although more than half were successfully grafted. All females and males who responded with the production of B cell cytotoxic antibodies monospecific or multispecific, with the exception of 1 female, demonstrated an allograft survival of greater than 1 year. In conclusion, differences between pre- and post-transfusion B cell PRAs and monospecific or multispecific HLA-DR antibodies identified in patient sera following transfusions were good predictors of renal allograft survival in both males and females.(ABSTRACT TRUNCATED AT 400 WORDS)