There is a growing list of chemicals that cause a low incidence of renal tumors in male rats, Upon acute exposure, some of these compounds cause a toxic syndrome in male rat kidneys that is referred to as u2u-globulin (U2u) nephrop athy (a2u-N)(Table 1), This syndrome is characterized by an excessive accumulation of protein droplets in lysosomes of proximal tubule epithelial cells, the presence of cellular casts at the junction of the proximal tubule and the thin loop of Henle, and regenerative tubules (1), The proximal tubule is a segment of the kidney nephron that can be divided into three distinct morphological segments, Ph P2, and P3 (Figure 1; 2), each with functional differences, The PI segment. and to a lesser extent the P2• is involved with active transport of ions resulting in the concentration of sub stances in the tubular fluid. The P2 segment in the rat has a well-developed lysosomal-phagosomal system, which contains relatively large dark-staining lysosomes, suggesting that this segment is important for the uptake and catabolism of proteins. The involvement of these large lysosomes in the