Peptides play roles in cell regulation and signaling and are regulated by peptidases, highly expressed in the kidney. Several peptide-convertases have been characterized as diagnostic and prognostic markers for solid tumors, including renal cancer; however little is known about their in vivo role in kidney tumors. The present study compares the activity of a range of peptidases in tumor and non-tumor tissues from clear-cell renal cell carcinoma (CCRCC) patients. Acid, neutral, basic and omega activities were selected. Clear-cell renal cell carcinoma displays a selective and restricted pattern of activities. Puromycin-sensitive aminopeptidase activity in the tumor increases (tumor (t) = 10,775 vs non-tumor (n) = 7,635 UP/mg protein; p<0.05) while aminopeptidase N decreases (t = 6,664 vs n = 33,381 UP/mg prot.; p<0.001). Aminopeptidase B activity of the particulate fraction in tumors decreases (t = 2,399 vs n = 13,536 UP/mg prot.; p<0.001) when compared with non-tumor tissues and aspartyl-aminopeptidase activity decreases significantly in CCRCC (t = 137 vs n = 223 UP/mg prot.; p<0.05). Soluble and particulate pyroglutamyl peptidase I, aminopeptidase A and soluble aminopeptidase B activities do not vary in renal cancer. The relative expression for the aforementioned peptidases increases in CCRCC for aminopeptidase B (1.5-fold), A (19-fold), aspartyl-aminopeptidase (3.9-fold), puromycin sensitive aminopeptidase (2.5-fold), and pyroglutamyl peptidase I (7.6-fold). Only aminopeptidase N expression decreases in tumors (1.3-fold). This peptidase profile in the neoplastic kidney suggests a specific role for the studied convertases and the possible involvement of an intracrine renin-angiotensin system in the pathogenesis of clear-cell renal cell carcinoma.