Histamine release may underline the side effects (particularly anaphylactoid) of radiographic contrast media. To study the histamine-releasing properties of radiographic contrast media, this study measured the in vitro release of histamine from human basophils incubated with diatrizoate, a standard ionic radiographic contrast agent, and with iopamidol, a newly developed non-ionic contrast agent. The basophils were separated from blood obtained from 16 patients scheduled for coronary angiography. For both diatrizoate and iopamidol, the concentration of histamine released varied as the concentration of radiographic contrast agent was increased from 0.075 M to 0.50 M. At the higher concentrations tested, the percent of histamine released by iopamidol was about half that released by diatrizoate (p less than 0.05). These data suggest that the use of non-ionic contrast media may involve less patient risk from the histamine-mediated allergic and/or hemodynamic side effects associated with radiographic contrast procedures.