The volume dependence of respiratory resistance (Rrs), usually observed during normal breathing, is expected to be accentuated during expiratory flow limitation (EFL). In order to quantify this dependence we studied the pressure, flow, and volume data obtained from eight New Zealand rabbits, artificially ventilated at different levels of applied expiratory pressure (0-10 hPa), before and during histamine i. v. infusion. EFL was provoked by lowering the expiratory pressure and was detected by the application of an additional negative expiratory pressure and by forced oscillations. The analysis of respiratory system mechanics was performed by multiple regression, using the classical linear first-order model and also a nonlinear model, accounting for volume dependence of Rrs. Both models satisfactorily fitted the data in the absence of EFL. The nonlinear model proved to be more appropriate in the presence of EFL. The coefficient expressing the volume dependence of Rrs (Rvd) was significantly more negative during EFL. Rvd values were highly correlated with the fraction of the tidal volume left to be expired at the onset of EFL. A threshold Rvd value of -1,000 (hPa x s x l(-2)) detected EFL with high sensitivity and specificity. We conclude that a strongly negative volume dependence of Rrs is a reliable and noninvasive index of EFL during artificial ventilation.