To examine the role of sialic acid in the respiratory tract, the influence of neuraminidase from Clostridium perfringens was investigated on contractions of isolated guinea-pig and rat trachea and on histamine release from guinea-pig lung tissue. Treatment with 2.0 units/ml of neuraminidase at 37 degrees C and pH 7.4 for 30 min caused an approximately 60% removal of total N-acetylneuraminic acid, a representative sialic acid, from muscle from guinea-pig and rat trachea. Neuraminidase concentration dependently induced histamine release from guinea-pig chopped lung tissue, but has no effect on contractions produced by acetylcholine, histamine and 5-hydroxytryptamine. Pretreatment with 2.0 units/ml of neuraminidase inhibited the contraction induced by antigen (ovalbumin) or compound 48/80. These findings suggest, at least in part, that sialic acids sensitive to neuraminidase are involved in the regulation of histamine release but not tracheal contraction.