Familial aggregation of cross-sectional pulmonary function was examined in 5,003 subjects from 1,408 families participating in the Framingham Study. Subjects, who were members of either the Original Cohort (recruited from 1948 to 1952) or the Offspring Cohort (recruited from 1971 to 1974), underwent spirometry at a mean age of 53 yr. The effects of age, height, weight, and smoking status on FEV1 were evaluated through linear-regression analysis, with separate models for men and women in each cohort. The gender- and cohort-specific standardized residual FEV1 from these models was used as the phenotypic variable in familial correlation and segregation analyses to assess inheritance patterns. In models that assumed no major gene determining FEV1, correlation of pulmonary function was greater for mothers and offspring than for fathers and offspring (ρ[mo] = 0.190, ρ[fo] = 0.112; p = 0.06), and sibling correlation exceeded parent-offspring correlation (ρ[sib] = 0.225; p < 0.01). By comparison with a general model, in which transmission probabilities and residual familial correlations are arbitrary, models that imposed a Mendelian gene were rejected (p < 0.001). A model with no parent-offspring transmission of a major factor, but with residual familial correlation, provided as good a fit as the general model, suggesting that environmental and/or poly genic genetic influences determine FEV1.