By mimicking hemostatic structural domains of collagen, Streptococcus sanguis (aggregation-positive phenotype; Agg⁺) induces platelets to aggregate in vitro. To test the hypothesis that aggregation occurs in vivo, S. sanguis (Agg⁺ or Agg suspension) was infused intravenously into rabbits. The extent of hemodynamic and cardiopulmonary changes and the fate of circulating platelets were Agg⁺ strain dose dependent. Within 45 to 50 s of the start of infusion, 40 × 10⁸ CFU of the Agg⁺ strain caused increased blood pressure. Thirty seconds after infusion, other changes occurred. Intermittent electrocardiographic abnormalities (13 of 15 rabbits), ST-segment depression (10 of 15 rabbits), and preventricular contractions (7 of 15 rabbits) manifested at 3 to 7 min, with frequencies dose dependent. Respiratory rate and cardiac contractility increased during this phase. Blood catecholamine concentration, thrombocytopenia, accumulation of ¹¹¹Indium-labeled platelets in the lungs, and ventricular axis deviation also showed dose dependency. Rabbits were unaffected by inoculation of an Agg strain. Therefore, Agg⁺ S. sanguis induced platelet aggregation in vitro. Platelet clots caused hemodynamic changes, acute pulmonary hypertension, and cardiac abnormalities, including ischemia.