Employment of mouthpiece and noseclips (MP + NC) has repeatedly been shown to increase tidal volume (VT), but its effect on respiratory frequency (f) and its subsets is controversial. The mechanisms accounting for this alteration in breathing pattern are poorly understood and may include stimulation of oral or nasal sensory receptors or alteration in the route of breathing. In this study we demonstrated that use of a MP + NC, compared with nonobtrusive measurement with a calibrated respiratory inductive plethysmograph, alters the majority of the volume and time indexes of breathing pattern, with increases in minute ventilation (P less than 0.01), VT (P less than 0.001), inspiratory time (TI, P less than 0.05), expiratory time (TE, P less than 0.05), mean inspiratory flow (P less than 0.05), and mean expiratory flow (P less than 0.05) and a decrease in f(P less than 0.05). Separating the potential mechanisms we found that when the respiratory route was not altered, independent oral stimulation (using an occluded MP) or nasal stimulation (by applying paper clips to the alae nasi) did not change the breathing pattern. In contrast, obligatory oral breathing without additional stimulation of the oral or nasal sensory receptors caused increases in VT (P less than 0.05), TI (P less than 0.05), and TE (P less than 0.01) and a fall in f(P less than 0.05). Heating and humidifying the inspired air did not prevent the alteration in breathing pattern with a MP. Thus change in the respiratory route is the major determinant of the alteration in breathing pattern with a MP + NC.