We evaluated the direct effects of a crude, water extract of cotton bract on tone in the isolated trachealis muscle of dogs and guinea pigs, and the effects of CBE on tension responses induced by electric field stimulation (EFS) of intrinsic excitatory and inhibitory nerves. CBE evoked contraction of both tissues, but in higher concentrations relaxed the guinea-pig trachealis. CBE potentiated EFS-induced contractions of dog trachealis but did not do so in the guinea-pig tissue. In contrast, CBE potentiated EFS-induced relaxations of guinea-pig trachealis, but had a negligible effect on such responses in the clog tissue. These results indicate that species differences exist in the effect of CBE on airway smooth muscle, and that there exists an effect of CBE on neurotransmission to the muscle which may influence the neural control of its tone.