The actions of lignocaine and tetrodotoxin (TTX) in a tracheal segment of the cat were tested on secretion of mucus macromolecules radiolabelled with 35S and 3H. Lignocaine, 4.3-43 mM, given into the segment, caused a concentration dependent increase of secretion of 3H-and 35S-labelled macromolecules. At 43 mM, lignocaine increased secretion: delta 3H = +433 +/- 191%, delta 35S = +327 +/- 34.5% (n = 8). This effect lessened over 15-45 min. Atropine (1 mg/kg) had little effect on these responses. All concentrations of lignocaine tested (4.3-43 mM) abolished the effect of vagus nerve stimulation on secretion and diminished the effect of a submaximal concentration of pilocarpine (5 microM) in the segment in a dose-dependent manner. TTX in the segment did not alter the resting secretion. At 50 microM it abolished, and at 10 microM diminished, vagal control of secretion without affecting the secretory response to pilocarpine. The study shows that lignocaine, in concentrations which block vagal control of secretion (greater than or equal to 4.3 mM), stimulates the release of mucus macromolecules. Resting secretion is unaltered by TTX, and so does not appear to be under neurogenic inhibition. Larger concentrations of lignocaine (greater than or equal to 13 mM) also diminish pilocarpine-induced secretion, whereas TTX may inhibit nervous control of mucus secretion selectively. The results suggest that clinical anaesthesia of the airways with lignocaine may stimulate mucus secretion.