Nonionic contrast media are suggested to cause increased thromboembolism (in vivo), platelet aggregation and procoagulant effect (in vitro) as compared with ionic contrast media. To study these effects in vivo, 30 consecutive patients undergoing routine angiography were prospectively randomized to three groups of 10 patients each. Group A received diatrizoate (ionic, high osmolality), Group B ioxaglate (ionic, low osmolality) and Group C iohexol (nonionic, low osmolality). In vivo platelet alpha-granule release and fibrin-1 formation were measured by radioimmunoassay of beta-thromboglobulin and fibrinopeptide A in peripheral venous samples. Levels were estimated at three stages during the procedure: before and after left ventriculography and after coronary angiography. No differences were noted (p = NS) when the ratios of beta-thromboglobulin and fibrinopeptide A were compared among the three groups. These data suggest that the newer nonionic contrast media do not demonstrate enhanced systemic platelet activation or fibrin formation as compared with standard ionic contrast media. However, larger randomized clinical studies are necessary to conclusively establish the suggested thromboembolic potential of nonionic contrast media.