Graft rejection remains the major problem complicating renal allograft transplantation. A reliable posttransplant predictor of impending rejection will be valuable to help maintain better graft function. We monitored 47 patients with end-stage renal disease treated by renal allograft starting 1 day pretransplantation and continuing for up to 90 days postgrafting. Peripheral blood mononuclear cells (PBMC) from both patients and 71 healthy subjects were compared for: (1) DNA synthesis in T and B lymphocytes in response to mitogens; (2) interleukin-2 (IL-2) production; (3) natural killer (NK) and antibody-dependent cell-mediated cytotoxic (ADCC) activities; (4) induced augmentation of NK and ADCC activities by the biological response modifiers (BRM), lymphoblastoid interferon, recombinant alpha-2-interferon, gamma-interferon and recombinant IL-2. During the 2 weeks preceding rejection we found lower than normal levels of IL-2 production (p less than 0.0005) and DNA synthesis (p less than 0.01) in concanavalin A-stimulated PBMC. IL-2 yield reached its lowest level on the day of rejection and increased sharply the following week after antirejection therapy was started. Mitogen-stimulated DNA synthesis rose in parallel with increasing levels of IL-2 production. Both NK and ADCC activities increased during rejection (p less than 0.05). The ADCC response to BRM activation measured during the first 2 weeks postgrafting was found to correlate with the stability of the graft. Recipients whose graft function remained stable had a minimal ADCC response to BRM.(ABSTRACT TRUNCATED AT 250 WORDS)