Acute rejection is the most important single risk factor for chronic renal allograft rejection. Numerical quantitation of rejection episodes does not take into account the intensity and length of these episodes, both of which may contribute to the severity of chronic rejection. We propose a single numerical parameter for the frequency, intensity and length of acute rejections, the "Area Under the Serum Creatinine versus Time Curve" (AUCCr) using renal allografts between inbred rat strains. Twenty-seven renal transplantations were performed from the DA to WF rat strain. The rats were immunosuppressed with 5 mg/kg body weight of CyA injected s.c. for 1, 2, 3 and 12 weeks, resulting in differing numbers (0-4) of biopsy-confirmed acute rejections of varying intensity (s-cre: 100-448 mumol/L) and length (3-24 days), all of which were reversed with additional CyA treatment. The intensity of chronic changes in graft histology was quantitated using the "Chronic Allograft Damage Index" (CADI). End-point transplant function was quantitated as level of serum creatinine at sacrifice. The AUCCr from 0 to 3 weeks (AUCCr0-3), encompassing the recovery period after operation, free of rejections, did not correlate with the CADI (r = 0.230, P = 0.249). All AUCCr from 3 weeks onwards correlated with the CADI. The best correlation with the CADI was obtained with AUCCr from 3 to 12 weeks (AUCCr3-12) (r = 0.922, P = 0.0001). This interval coincides with the timing of all acute rejection episodes. AUCCr3-12 correlated equally well to end-point transplant function (r = 0.890, P = 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)