In a system of rigid tubes under steady flow conditions, the coefficient of friction [CF = 2 delta P/(rho V2/A2)] (where delta P is pressure drop, rho is density, V is flow, and A is cross-sectional area) should be a unique function of Reynolds' number (Re). Recently it has been shown that at any given Re, the value of CF using transpulmonary pressure (PL) was lower when breathing He-O2 compared with air (Lisboa et al., J. Appl. Physiol.: Respirat. Environ. Exercise Physiol. 48: 878-885, 1980). One explanation for this discontinuity is that PL includes the pressure drop due to tissue viscance, which is independent of V, and thus would lead to an overestimate of CF on air compared with He-O2 at any Re. We tested this hypothesis by measuring V related to alveolar pressure, rather than PL, in normal subjects breathing air, He-O2, and SF6-O2. In each subject, for a given Re, CF was greatest breathing SF6-O2 and lowest breathing He-O2, similar to results using PL. Thus tissue viscance is not the sole cause of the discontinuous plot of CF vs. Re, and this phenomenon must be due to other factors, such as changing geometry or nonsteady behavior.