Responses of various preparations of guinea pig and rat airways to synthetic porcine neuropeptide Y were analysed in vitro. NPY in doses up to 10(-6) M, induced a dose dependent contraction in trachea, bronchi and lung parenchymal strips of the guinea pig but did not have any effect in similar preparations obtained from the rat. In guinea pig airways the contractile responses to NPY were small in size and characterized by a slow onset and a long duration. This effect of the peptide was not dependent on pre-junctional nerve stimulation but rather mediated through the secondary generation of cyclooxygenase products. It is concluded that NPY may contribute per se to regulating the resting tone of guinea pig airways.