The urinary excretion of four enzymes (alkaline phosphatase: AP, leucine aminopeptidase: LAP, lactate dehydrogenase: LDH, muramidase: M) was measured in unanesthetized adult male Wistar rats within 48 h after either a single injection of mercuric chloride (HgCl2) (0.5-1.0 mg x kg-1), or of gentamicin (2.5-25 mg x kg-1), or of tobramoycin (2.5-25 mg x kg-1), or after 30 min of clamping of both renal arteries. Glomerular filtration rate (GFR), TmPAH, plasma urea, urinary protein and sodium excretion were measured simultaneously. The excretion of AP, LAP and LDH, but not that of M, increased significantly above control levels after renal ischemia or the nephrotoxic agents; the increase was dose-related after HgCl2. GFR was not depressed, but TmPAH decreased after the higher doses of the toxic agents. Though more sensitive for detecting minor grades of acute renal damage than function tests, measurements of urinary enzyme excretion were fraught with large inter-individual variation, and variable time-course of changes in different types of renal damage. Short-term exposure (3 months) to phenylmercuric acetate was associated with a significant decrease of the urinary excretion of AP, and of LAP, and of AP activity measured histochemically in proximal tubular cells.