The synthesis of prostacyclin (PGI2) was studied in isolated perfused rat lungs during the infusion of radiographic contrast media into the pulmonary circulation. At the same molar concentration, diatrizoate, iopamidol, and NaCl fairly equally stimulated the generation of PGI2. A bolus injection of histamine also enhanced the formation of PGI2. A high dose of ionic diatrizoate and hypertonic saline (0.4 mol/l) caused considerable pulmonary edema, which was less marked with non-ionic iopamidol. Experiments with 125I-labeled contrast media indicated rapid efflux of contrast media from the lungs. The present investigation indicates that different contrast media stimulate the synthesis of prostacyclin mainly because of chemical irritation of the pulmonary endothelium. The enhanced formation of endothelium-derived prostacyclin may mediate some systemic and local side effects seen temporarily during intravascular contrast medium examinations.