To determine the importance of genetic influence on the variability of maximum expiratory flow-volume (MEFV) curves in normal individuals, MEFV curves breathing air and a mixture of 80% helium and 20% oxygen (He-O2), lung volumes, specific airway conductance, and closing capacity (CC) were obtained in 10 pairs of identical and 6 pairs of nonidentical twins, all nonsmokers and asymptomatic. For a given pair of identical twins, MEFV curves on air were more similar than those of a pair of nonidentical twins (P less than 0.02). The intrapair differences of identical twins were smaller than nonidentical twins of maximum expiratory flow (Vmax) at 60% of total lung capacity (TLC) on air (P less than 0.001) and on He-O2 (P less than 0.01). However, intrapair differences of Vmax at 40% TLC and CC were not significantly different in the two groups. Since Vmax at 60% TLC on air and He-O2 are dependent on the geometry of large airways these findings are suggestive that the geometry of large airways may be related to genetic factors. The relationship of the geometry of the peripheral airways and genetic factors has not been defined.