The chemistry of low-osmolality contrast agents is reviewed, the effects of these agents on vascular and organ physiology are compared with the effects of conventional ionic contrast media, and guidelines for intravascular use of the low-osmolality agents in selected high-risk patients are presented. Three low-osmolality contrast agents, the nonionic media iohexol (Omnipaque, Winthrop-Breon) and iopamidol (Isovue, Squibb) and the dimeric medium ioxaglate meglumine-sodium (Hexabrix, Mallinckrodt) have recently been introduced into the contrast-media market. Compared with conventional ionic contrast media, these new agents demonstrate approximately one third of the osmolality per given iodine concentration (degree of roentgenographic opacification). Therefore, the risks of hyperosmolarity-induced reactions to contrast media are lower with the new agents. The low-osmolality agents may be associated with a reduced incidence of contrast-media-induced hypersensitivity reactions. Because of their lower osmolality, these agents produce less vessel dilation, vascular endothelial damage, and associated pain and discomfort than equi-iodine concentrations of the conventional ionic media. They also demonstrate a reduction in the incidence and severity of contrast-media-induced renal vasoconstriction and proteinuria, hemodynamic alterations, negative chronotropic effects, depression of myocardial contractility, and neurotoxicity in the presence of an altered blood-brain barrier. These low-osmolality agents produce fewer undesirable physiological effects than conventional contrast agents, but the cost of the new products can be more than 10 times as great. Therefore, the new products should be used selectively in patients known to be at increased risk for reactions to intravascular contrast media. A scoring system was developed to permit rapid recognition of documented single or multiple risk factors and subsequent determination of whether to administer a low-osmolality agent.