The acute hemodynamic effect of intravenous administration of polystyrene microspheres was investigated and correlated with their distribution pattern and kinetics. Microspheres of three diameters (3.4, 7.4, and 11.6 micrometer) were administered. The 7.4- and 11.6-micrometer diameter microspheres were filtered by the pulmonary capillary network following intravenous administration, the majority during the first pass. There was no significant hemodynamic effect following administrations of the 7.4- and 11.6-micrometer diameter microspheres in doses as high as 3.0 X 10(9) and 6.1 X 10(8) respectively (total cross-sectional area of 1.3 X 10(11) and 6.4 X 10(10) micrometer2, respectively). Intravenous administration of 3.4-micrometer diameter microspheres produced significant dose-dependent systemic hypotension and depression of myocardial performance at dosages as slow as 1.0 X 10(10) (cross-sectional area of 9.1 X 10(10) micrometer2). These differences in acute hemodynamic effect from the 7.4- and 11.6-micrometer diameter microspheres may be due to the differences in distribution kinetics and fate of the 3.4-micrometer diameter microspheres, which readily pass through the lungs to the spleen. Although elimination of the smaller spheres from the blood during the first 6-8 min was rapid, i.e., t 1/2 = 1.62 and 1.72 min from the venous and arterial blood circulation, respectively, levels of 10(3) spheres/g of blood were present in the circulation for greater than 1 hr. These findings must be considered in the planning of intravenous administration of microspheres as a drug delivery system to target organs.