The aims of this study were to determine whether renal functional reserve (RFR) is still present in cyclosporin-treated renal transplant recipients, and to examine the relationship between RFR and proximal reabsorption. A serial study was carried out in 12 renal allograft recipients (R) with good renal graft function at 20 +/- 2.5 days (S1) and at 7.6 +/- 0.4 months (S2) post-transplantation, and the results were compared to those in eight subjects who had undergone unine-phrectomy (one-kidney controls: UNx.C) and in 12 healthy volunteers (two-kidney controls: 2K.C). R and C were in similar sodium and protein balance and with similar plasma renin and aldosterone levels. R had normal serum creatinine level on moderate doses of cyclosporin (whole blood cyclosporin concentration: 212 +/- 20 and 125 +/- 20 ng/ml at S1 and S2, respectively). Eight one-hour clearance periods were performed prior to, during and following a three-hour i.v. infusion of a mixture of 20 l-amino acids (Azonutril 25, 4.5 mg amino acids/kg/min). Baseline glomerular filtration rate (GFR) was lower in recipients at S1 and S2 (55 +/- 5 and 54 +/- 4 ml/min/1.73 m2, respectively) than in UNx.C and 2K.C (72 +/- 4 and 113 +/- 4 ml/min/1.73 m2, respectively, P < 0.05 and 0.001). Amino acid infusion elicited significant GFR increases in controls as well as in recipients in spite of higher renal vascular resistances (RVR). The greater measured increase in GFR, which represented RFR, was 18 +/- 3 and 28 +/- 2 ml/min/1.73 m2 in UNx.C and 2K.C, respectively (P < 0.001), and 17 +/- 3 ml/min/1.73 m2 in R at both S1 and S2 (P < 0.001). Contrary to both UNx and 2K controls, the acute hyperfiltration in R at S1 and S2 occurred with a significant increase in effective renal plasma flow, no alteration in filtration fraction and a large decrease (approximately 20 and 17%) in RVR while no correlation could be detected between the RFR and baseline GFR. Baseline lithium clearance, used as a marker of overall proximal fluid delivery (CLi), was significantly lower, whereas baseline fractional excretion of lithium (FELi) was significantly higher in R at S1 and S2 and in UNx.C (41 +/- 4, 40 +/- 3 and 38 +/- 3%, respectively) than in 2K.C (31 +/- 2%, P < 0.05). Consistent and significant increase in CLi, FELi and absolute proximal reabsorption occurred both in R at S1 and S2 and in UNx and 2K controls during elicitation of RFR.(ABSTRACT TRUNCATED AT 400 WORDS)