To investigate in vivo and in vitro microaggregation in coronary artery disease, we obtained blood samples from the coronary sinus (CS), pulmonary artery (PA), and aorta (AO) in patients undergoing cardiac catheterization. An electronic particle size analyzer was used to quantify microaggregates 13 to 81 mu in diameter in blood. In the first group of 58 patients, preformed circulating microaggregates and platelet responsiveness to ADP were assessed in AO and PA blood only. The coronary artery disease patients did not have significantly higher volumes of preformed in vivo aggregates in either AO or PA blood. However, the mean aggregate size in response to 0.2 microM ADP in vitro was larger in both AO and PA blood in patients with coronary disease [12.4 +/- 0.9 vs. 9.4 +/- 1.4 X 10(3) mu3 (AO); 12.5 +/- 0.9 vs. 8.3 +/- 0.7 0.7 X 10(3) mu3 (PA)]. In a second group of 46 patients, CS, AO and PA samples were compared using the same methods. The volume of microaggregates preformed in vivo was significantly greater in CS blood than in PA or AO blood in patients with and without coronary disease. The volume and mean size of aggregates induced by ADP in vitro were smaller in CS blood compared to PA. In conclusion, the volume of in vivo microaggregates is increased in CS blood, independent of coronary disease, but significant volumes are not found in PA or AO blood. Patients with coronary disease have more reactive platelets to in vitro aggregatory agents in AO and PA samples of similar hematocrit.