The histamine liberation caused by the incubation of rat peritoneal mast cells with solutions of methylglucamine salts of acetrizoate, diatrizoate, iothalamate, and iodipamide was determined. All of the contrast media were shown to be capable of liberating histamine from the mast cells at final concentrations (after dilution with mast cell suspensions) ranging from 5 to 40% w/v. On a weight per volume concentration basis, acetrizoate and iodipamide were the most potent histamine liberators while iothalamate and diatrizoate were the least potent. On an osmolality basis, acetrizoate and iodipamide produced virtually identical histamine release. The methylglucamine ion (when tested as methylglucamine hydrochloride) slightly but consistently inhibited the release of histamine relative to the “spontaneous” release occurring in the neutral buffer control solution.