(1->3)-b-D-glucans are a diverse family of glucose polymers. They have been shown to mediate effects on the respiratory system, including influx of inflammatory cells and release of inflammatory mediators. It is believed that these pharmacological activities are dependent on the molecular weight, degree of branching, tertiary structure and solubility of the glucan. In order to further define the effect of (1->3)-b-D-glucans on the respiratory system, this present study evaluates whether these agents can alter the bronchoconstrictor activity of methacholine on airway smooth muscle in the guinea pig. Perfused lung and immersed tracheal tissue preparations were exposed to various doses of methacholine in the prescence of a variety of (1->3)-b-D-glucans, and the resultant bronchoconstrictor activity was determined. Both insoluble and soluble (1->3)-b-D-glucans reduced the contractor activity of methacholine on the tracheal smooth muscle. However, in the perfused lung preparation, only the soluble (1->3)-b-D-glucans promoted a decrease in response to methacholine. These results imply that the (1->3)-b-D-glucans may act by different mechanisms in these two respiratory tissues.