The effects of intracoronary injection of two nonionic contrast media (iohexol and metrizamide) on myocardial contraction and chemical composition of coronary sinus (CS) blood were compared with those caused by the standard ionic contrast material for coronary angiography, sodium meglumine diatrizoate (R76), in 14 anesthetized dogs. The effects of each agent on regional contractility were compared in the normal state and in the presence of a critical coronary artery stenosis. The three contrast media produced equivalent decreases in hematocrit and sodium (both NS), but R76 caused a greater increase in CS osmolality (p less than 0.02). R76 caused a significant decrease in CS potassium and ionized calcium (both p less than 0.001), but neither nonionic contrast medium caused a significant change in either potassium or calcium. In the normal state, R76 caused initial transient (less than 10 seconds) increases in both end-diastolic (p less than 0.006) and end-systolic segment length (p less than 0.02) and a decrease in rate of change of segment length (dL/dt) (p less than 0.002). The nonionic agents caused a mild increase in dL/dt (p less than 0.04) and a decrease in end-systolic segment length (p less than 0.03); both returned to control levels within 1 minute. In the presence of a stenosis, R76 caused a more severe and prolonged increase in end-diastolic and end-systolic segment lengths (p less than 0.03) and a decrease in dL/dt (p less than 0.002), which did not return to control within 2 minutes. The effects of the nonionic agents were similar in both normal and diseased states. We conclude that nonionic contrast media produce fewer alterations than ionic contrast media in coronary sinus blood chemistry and myocardial contractile state. The effect of ionic contrast media on regional contraction is accentuated in the presence of coronary artery stenosis.