The mechanical activity of proximal airways isolated from human lung specimens obtained at autopsy from 11 neonates was studied in response to the following compounds: carbachol, histamine, potassium chloride (KCl), neurokinin A (NKA) (both in the presence and in the absence of the neutral endopeptidase inhibitor phosphoramidon) and isoproterenol. Isometric responses to the various concentrations of each of the compounds were expressed as both raw values of force normalized to smooth muscle cross-sectional area (SMCSA), i.e., muscle stress and percentages of the maximal response to acetylcholine. Maximal active muscle stress of human neonatal bronchi was induced by carbachol and averaged 95 +/- 25 mN/mm2 SMCSA (n = 8). The rank of maximal force induced by the contractile agonists was carbachol > histamine > KCl > NKA, and the rank of the concentration of drug producing one-half of the maximum effect (EC50) was NKA < carbachol < histamine < KCl. The EC50 value for isoproterenol was the lowest, although it generated the smallest mechanical response. When compared with results obtained under identical experimental conditions in the human adult lung, except for carbachol and isoproterenol, general trends were an increase in force generation with age and little changes in EC50 values. There was a decrease in carbachol-induced force with age, whereas the opposite was observed with isoproterenol. We conclude that most of the mechanisms that control airway tone in humans are already present in the neonate. Alterations in the response to agonists with the maturational process may have implications in the pharmacologic modulation of bronchial obstruction in neonates.