We examined familial resemblance and performed segregation analysis for the maximal expiratory flow rate at 50% of vital capacity (Vmax50) and the ratio of Vmax50 to forced vital capacity (FVC), based on data from 309 nuclear families with 1,045 individuals in the town of Humboldt, Saskatchewan, in 1993. Vmax50 is considered as an index of airway function and Vmax50/FVC is considered as an index of airway-parenchymal dysanapsis. Both Vmax50 and Vmax50/FVC were preadjusted for host characteristics (age, height, and weight), environmental factors, and history of respiratory symptoms and diseases in four separate groups (mothers, fathers, daughters, and sons). Both Vmax50 and Vmax50/FVC showed low father-mother correlations and significant parent-offspring and sibling-sibling correlations. Segregation analysis indicated that for residual Vmax50, the model of no-parent-offspring transmission with possible heterogeneity between two generations fitted the data as well as did the general model with arbitrary transmission probabilities. The Mendelian hypothesis for Vmax50 was rejected, which was consistent with our previous findings for other indexes of airway function. For residual Vmax50/FVC, however, a single locus explained all the familial resemblance and both no-parent-offspring-transmission hypotheses [tau(AA) = tau(AB) = tau(BB) = qA and tau(AA) = tau(AB) = tau(BB)] were rejected. The study provides evidence for a single locus influencing airway-parenchymal dysanapsis.