The ratio of urine protein/urine creatinine in spot urine specimens was measured to determine the influence of steroid withdrawal and other clinical variables on urinary protein excretion in 135 primary renal transplant recipients, including 73 patients in whom steroid withdrawal was never attempted and 62 patients in whom steroid withdrawal was attempted at various times following transplantation. Both univariate and multivariate analyses showed that steroid withdrawal per se did not directly influence proteinuria. However, patients who renewed steroid therapy because of acute allograft rejection following attempted steroid withdrawal exhibited significantly more proteinuria than was encountered either in patients who remained steroid-free or in those for whom steroid withdrawal was never attempted. This study suggests that steroid withdrawal itself does not lead to proteinuria, however, acute rejection following steroid withdrawal clearly accelerates urinary protein excretion that may be the harbinger of chronic allograft rejection.