. Differences between samples were considered to be significant at P,0.05. ~~ Airway smooth muscle contraction is mainly controlled by autonomic neurons innervating the airways and the lung. The autonomic nerves regulate many critical aspects of airway function, e.g. ASM tone, mucus PNU-100480 chemical information secretion and bronchial microcirculation. The autonomic nerves are subdivided into parasympathetic-cholinergic, sympathetic-adrenergic and nonadrenergic non-cholinergic nerves. Several previous studies indicate that the innervation of the lung differs considerably between and within species. For instance, the relative tissue content of the neuropeptides substance P and calcitonin gene related peptide is much higher in guinea pigs than in rabbits or marmosets. Concerning acetylcholine, rat tracheas store about tenfold more of the neurotransmitter than guinea pig trachea or human bronchi. Neurotransmission can also be modulated differently, e.g. cholinergic neurotransmission is facilitated by neurokinin receptors in rabbit and guinea pig airways, whereas those receptors have no effect in human airways. Within one species, the same neuropeptides can have opposing effects. Substance P or neurokinin A cause bronchorelaxation in tracheal preparations from Sprague-Dawley and Wistar rats, but contract those from Fischer 344 rats. Consequently, lung innervation is heterogeneous and extrapolation of 
pharmacological interventions from laboratory animals to the human situation is difficult. Given all these problems it appears important to identify an experimental animal model that reflects the human situation. An established ex vivo model to study bronchoconstriction in different species is the technique of precision-cut lung slices 1 Neuronally Airway Control in Different Mammals . PCLS were initially introduced for the study of airway pharmacology in rats. Since then this method has been adopted for other species such as mice, guinea pigs, horses, sheep, non-human primates and humans. PCLS are highly useful in pharmacological and toxicological studies. PCLS, that preserve the respiratory tract both morphologically and functionally, have several advantages: First, airway contractions are auxotonic since airways are embedded in their surrounding tissue. Second, contractions of vessels and airways can be distinguished. Third, many slices are obtained from one subject, thereby reducing the number of animals and providing the opportunity of an internal control. Fourth, small and large airways are accessible. Using this approach we showed that with respect to bronchoconstriction small airways compared to large airways are more sensitive to methacholine, serotonin, the thromboxane prostanoid receptor agonist U46619 and allergens in lungs of different species. On the other hand, at least in rats, small airways are less sensitive to EFS than large airways. The present study was designed to systematically study the neuronally mediated airway constriction in different mammals. The use of identical experimental conditions permitted a high degree of comparability among the species studied: mouse, rat, guinea pig, sheep, marmoset and human. Our findings show remarkable differences between all species and suggest that guinea pig PCLS are the best approach to study neuronal mechanisms of airway tone regulation relevant to humans based on the current results. PCLS PCLS were prepared as previously described and used one day after preparation. Briefly, whole lungs or lung lobes were fil