In several models of acute renal failure (ARF) in animals, acidosis has been found to worsen the renal failure, whereas alkalosis may ameliorate it. Most evidence points to a reduction in the degree of tubular obstruction by casts as the explanation for the beneficial effects of bicarbonate administration. However, alkalinization of the urine is effective only in some experimental conditions but not in others. The reason for these differences is not known but may relate to the nature of the obstructing casts. Alkalinization of the urine could decrease cast formation in Bence-Jones protein and hemoglobinuric ARF by increasing the negative charge on these molecules, thereby diminishing precipitation with anionic Tamm-Horsfall protein. In contrast, release of tubular cell contents into the urine, as occurs in renal ischemia, could lead to complex casts not responsive to alterations in urine pH. In aminoglycoside ARF, the beneficial effects of urine alkalinization may be due primarily to reduced uptake of the antibiotic by tubular epithelium, resulting in less cellular damage. Because tubular obstruction reduces net filtration pressure, new approaches to therapy which include efforts to raise net glomerular filtration pressure may improve the therapeutic efficacy of alkali administration.