To evaluate the consequences of breathing pattern variations inherent to lung disease on the rebreathing measurement of lung tissue volume (Vt), we carried out a study of ten normal human subjects in whom we assessed the effects of changes in rebreathing volume (Vreb), additional deadspace volume (AVD), respiratory rate (RR), and body height. Vt and alveolar volume (VA) were determined from the end-tidal concentrations of acetylene and helium. We performed Vt measurements using different combinations of Vreb (20, 30 and 50% of predicted vital capacity), of AVD (0, 100, and 200 ml) and of RR (10, 25, and 40 br.min-1). Only slow RR (10 br.min-1) resulted in a higher Vt (p less than 0.001). An increase in Vreb induced an increase in VA but not in Vt. VA and Vt were positively correlated with the height of the subjects. We conclude that, in normal subjects, Vt increases: 1) with the height of subjects; and 2) when the respiratory rate is low. Interpretation of Vt results must take into account these two variables.