Hyperlipidemia and thrombocytopenia are well recognized side effects of use of sirolimus. Little is known about occurrence of proteinuria with sirolimus use. This study was carried out between May 2001 through June 2002 and included 80 live–donor renal allotransplant recipients. The patients were stratified into 2 equal demographically matched groups to receive either sirolimus (5 mg) + steroids + low dose tacrolimus (Group A) or sirolimus (10 mg) + steroids + mycophenolate mofetil (Group B). Both groups received basiliximab induction therapy. 24 hour urinary protein quantification was carried out on regular time points. Histopathologic examination of renal allografts was carried out for those who experienced nephrotic range proteinuria in addition to one-year protocol biopsy at the end of follow up (one year). Nine patients in group A (22.5%), and 14 patients in groub B (35%) suffered from prteinuria (more than one gram per day)..Among them, nephrotic range quantification was found in 5 and 6 patients of group A and B respectively. Among group A, two patients had de novo glomerulonephritis (GN),One patient had recurrent FSGS and two cases of acute tacrolimus toxicity were found to have nephrotic range proteinuria.Among group B,3 patients were found to have de novo FSGS while another 3 patients had recurrent original disease.Renal allograft tissue protocol biopsies at one year revealed presence of glomerular sclerosis in 12% and 30.8% of group A and B respectively. Proteinuria as a possible cmplication of sirolimus treatment needs further evaluation including immunoflouresence and electron microscopy.