Release of substance P (SP) and neurokinin A (NKA), was demonstrated in the isolated perfused guinea-pig lung. Significant release was obtained by perfusion with capsaicin, high potassium, histamine, bradykinin dimethylphenylpiperazinium, and by electrical vagal nerve stimulation. Capsaicin-induced peptide release was not blocked by 1 microM clonidine. SP and NKA contracted respiratory smooth muscle, NKA being 42 times more potent. Both tachykinins were equipotent in relaxing pulmonary artery. It is concluded that multiple tachykinin can be released from capsaicin-sensitive sensory nerves in the respiratory tract, exerting multiple effects on the target tissues.