Buffered solutions of the sodium salts of iodipamide, acetrizoate, diatrizoate and iothalamalc were incubated with mast cells harvested from the peritoneal cavity of rats and the resultant histamine release was determined. The results of this study indicate that the sodium salts of these contrast media are capable of causing histamine liberation from rat peritoneal mast cells. Sodium iodipamide is the most effective, sodium iothalamate is the least effective and sodium acetrizoate and sodium diatrizoate are intermediate in their histamine liberating properties. Of the intermediate compounds, sodium acetrizoatc appears to be a slightly more effective histamine liberator than sodium diatrizoate. Studies with dextrose and sodium chloride solutions indicate that the histamine release from the mast cells is not due to the osmolality of the solutions nor to the concentration of the sodium ions present.