Prominent cytoplasmic vacuoles in renal tubular epithelial cells of the outer medulla were observed in several kidneys from test article-dosed mice during routine light microscopic (LM) examination. Because the vacuolar change was seen infrequently by LM examination, and was not found in any control mice from that study, it was not clear whether the vacuolation represented a drug-induced change. To address this question, kidney sections from multiple unrelated mouse studies (214 control mice and 541 test article-dosed mice representing six different compounds) were examined by LM for similar vacuolar changes. Vacuolation was seen by LM in 2.3% of the control and 2.8% of the test article-dosed mice. Transmission electron microscopy (TEM) was performed on kidneys with prominent vacuoles seen by LM in 5 control mice and 2 test article-dosed mice to further characterize the vacuoles. Additionally, kidneys from 4 randomly selected control mice lacking vacuolation by LM were examined by TEM. Samples from the outer medulla of kidney that had been fixed by immersion in 10% formalin were post-fixed in 2.5% glutaraldehyde and 2% osmium tetroxide and processed routinely for TEM.