The present study has established a method for obtaining low-frequency forced oscillation measurements of lung mechanics in the absence of neuromuscular blockade in the rat. Increasing the ventilation rate of the animals inhibited the spontaneous breathing of the animals for a short period of time; enough to make the low-frequency forced oscillation measurements of lung mechanics without the need for paralysis of the animals. Using this technique, it was possible to show that neuromuscular blockade with pancuronium bromide (0.4 mg/kg iv) resulted in a significant inhibition of methacholine responses in the parenchymal, but not the airway components of the rat lung. In studies where the animals were examined in a repeated manner, there was no significant difference in methacholine responses on day 3 compared with those obtained on day 1. Similarly, in animals that were both challenged with methacholine and lavaged, there was no significant difference in the methacholine responses or in the total and differential cell numbers obtained from the bronchoalveolar lavage fluid. Thus, this study presents a technique for obtaining low-frequency forced oscillation estimates of lung mechanics in non-paralysed rats and allows for repeated measures to be made in the same animals. In addition, this study has demonstrated that neuromuscular blockade has differential effects on methacholine responses in different parts of the lung. (C) 1999 Academic Press.