In the isolated perfused guinea-pig lung, lung resistance (RL) and dynamic compliance (CDYN) as well as flow, pH, PO2 and PCO2 of the perfusate were recorded. The baseline values were stable up to 2.5 h. Mean values (+/- SEM) for RL and CDYN were 0.36 cm H2O ml-1 s-1 +/- 0.04 and 0.27 ml cm-1 H2O +/- 0.02, respectively, which agree with in vivo values reported for unanaesthetized guinea-pigs. The pH was always slightly raised and the PCO2 always lowered in the effluent compared to the inflowing medium (P less than 0.001), indicating that the lung had an operative ventilation. Intravascularly administered acetylcholine, histamine and adenosine caused reproducible dose-dependent bronchoconstrictions recorded as increased RL and decreased CDYN. It is noteworthy that adenosine in this model and in vivo consistently produced bronchoconstriction which is in contrast to findings in other in vitro airway preparations. We conclude that this isolated perfused guinea-pig lung preparation has stable in vivo-like characteristics offering interesting possibilities for combining studies of respiratory effects with, for example, metabolism, pharmacokinetic and vascular reactivity studies.