We have examined peripheral circulatory variables that might contribute to the decrease in cardiac output and arterial pressure characteristic of anaphylactic shock. In six dogs instrumented with a right heart bypass, the intravenous administration of Ascaris suum antigen caused a 53% decrease in cardiac output and a 58% decrease in arterial pressure. Resistance to venous return increased from 0.0038 +/- 0.0004 to 0.0056 +/- 0.0006 mmHg X ml-1 X min (P less than 0.05), mean systemic pressure decreased from 7.0 +/- 0.6 to 4.4 +/- mmHg (P less than 0.005), and vascular compliance did not change. Assuming a constant vascular volume, the decrease in mean systemic pressure could be explained by a rightward shift of the systemic pressure volume curve. This constant-volume assumption was tested in intact (n = 6) and splenectomized dogs (n = 7). Serial measurements of protein oncotic pressure and hematocrit were used to estimate plasma volume changes during anaphylaxis. Both methods for estimating volume showed small increases in plasma volume at the time of the largest decrease in arterial pressure in both groups of animals. These results suggest that the primary circulatory mechanisms responsible for anaphylactic shock are an increase in resistance to venous return and a shift of the systemic pressure volume curve and not an acute loss of plasma volume.