The relationship between trypsin-inhibitory activity (TIA) and the nephrotoxic effects of mercuric chloride (HgCl2)--as illustrated by proteinuria and by a drop in the glomerular filtration rate (GFR) measured by creatinine clearance test (CCT)--was investigated in Wistar rats. HgCl2, 150 or 250 micrograms/100 g BW per day was injected intraperitoneally three times a week for 2 weeks. Both groups showed a significant degree of proteinuria and urinary TIA. Group B (250 micrograms HgCl2/100 g BW) displayed a greater drop in GFR than group A (150 micrograms HgCl2/100 g BW). The urinary TIA was significantly correlated with proteinuria (group A: r = 0.87, group B: r = 0.84), but it was also significantly inversely correlated with the CCT (A: r = -0.96; B: r = -0.88). CONCLUSIONS these results suggest that increased urinary TIA may be involved in and indicative of the pathogenesis of mercuric chloride induced nephrotoxicity.