Morphologic studies on the effect of dehydration on contrast media (CM)-induced renal changes were done. Sixty-six healthy Wistar rats were deprived of water for 24 hours before the intravenous (i.v.) injection of 1.0 or 3.0 g iodine (I)/kg of high-osmolal diatrizoate, low-osmolal iopromide or iohexol, iso-osmolal iotrolan, or 0.2 or 0.6 g/kg of high-osmolal magnetic contrast agent, gadolinium-DTPA (Gd-DTPA). Control animals received physiologic saline. After 2 hours, the kidneys were fixed by perfusion for light and electron microscopy, and the morphologic changes were semi-quantitatively reviewed by two independent observers blinded to the treatment. The smaller dose of iohexol or iotrolan and the larger dose of all the CM induced in the proximal convoluted tubule (PCT) cells a statistically highly significant (P less than .001) or significant (Gd-DTPA; P less than .01) cytoplasmic vacuolization. The changes were most prominent (P less than .001) after treatment with iohexol and iotrolan. The results might be related to the higher urinary CM concentration after low- and iso-osmolal agents. Dehydration further potentiates higher CM concentration. The morphologic injury, when compared with the author's earlier findings on normal rats, was clearly intensified by dehydration.