During a systematic evaluation of stable renal transplant recipients, we noted a marked discrepancy between the inulin and creatinine clearance values. The C(Cr)/C(In) ratio was 1.02 ± 0.02 in 'normal' subjects and 1.47 ± 0.15 in 20 transplant recipients. The C(Cr)/C(In) ratio of 14 living related recipients (1.51 ± 0.08) was not significantly different from that of cadaver recipients (1.37 ± 0.04). Evaluation of ten paired donors and recipients demonstrated a C(Cr)/C(In) ratio of 1.34 ± 0.06 and 1.51 ± 0.10, respectively (NS). In three donors, the C(Cr)/C(In) was 1.04 ± 0.02 before nephrectomy and 1.25 ± 0.08, 1 week after nephrectomy. The ratio in the recipients was 1.45 ± 0.13 1 week after transplantation. Other markers of glomerular filtration, urea and iodothalamate (Io), were evaluated. C(urea)/C(Cr) ratios were similar in normals, donors, and recipients (0.62, 0.62, 0.55, respectively). The C(urea)/C(In) ratio was 0.63 in normal subjects; it was, however, 0.72 ± 0.05 in donors and 0.9 ± 0.06 in recipients. C(Io)/C(Cr) and C(Io)/C(In) ratios in normal subjects were the same at 1.02 ± .04. C(Io)/C(Cr) ratio was 0.95 ± 0.04 in recipients and 0.96 ± 0.03 in donors. The C(Io)/C(In) ratio was 1.43 ± 0.08 in recipients and 1.23 ± 0.04 in donors. The data reveal a marked discrepancy between C(Cr) and C(In) in renal transplant recipients whether living related donors, were used. Furthermore, this discrepancy is manifest by 1 week after transplantation in both donors and recipients. Our data suggest that increased creatinine secretion is not solely responsible for this discrepancy, and that there may be an impairment to filtration of inulin at the level of the glomerulus. Back diffusion of filtered inulin, although unlikely cannot be ruled out from the present data.