Proportional assist ventilation (PAV) is a new mode of assisted ventilation which, by applying pressure in proportion to volume (volume assist, VA) and flow (flow assist, FA), should specifically reduce the inspiratory effort needed to overcome respiratory system elastance (Ers) and resistance (Rrs), respectively. The aims of this study were to determine (1) the effects of varying the level of VA on breathing pattern, inspiratory effort, and work of breathing, and (2) the interaction between VA and FA. In eight intubated patients with acute respiratory failure, four levels of VA (20 to 80% Ers) with and without a fixed amount of FA (approximately 50% Rrs) were evaluated. Compared with spontaneous breathing, VA increased tidal volume (VT) while respiratory rate (RR) was unchanged or fell slightly. The increase in minute ventilation (VE) was small and not significant. The addition of FA further increased VT while RR was significantly reduced so that VE remained unchanged. Increasing VA produced a graded reduction in inspiratory effort, reflected by decreases in the pressure-time integral of the diaphragm and the inspiratory muscles. These were further reduced when FA was added. VA decreased the elastic work of breathing (Wel) whereas resistive work (Wres) tended to increase so that the fall in total work (W/tot) was less than expected. At each VA setting, the addition of FA significantly reduced Wres and, as a result, Wtot. These results demonstrate that PAV can improve breathing pattern while reducing inspiratory effort by specifically decreasing Wel and Wres, and that VA and FA should be used together to optimize reductions in Wtot and the efficacy of assistance provided.