Besides environmental triggers, a family history of asthma is a strong risk factor for the development of asthma in offspring. The pooled data from 13,963 interviews of randomly selected, 20 to 48 yr-old participants from the 30 centers of the European Community Respiratory Health Survey (ECRHS) were analyzed with conventional logistic regression and a Class A regressive model adapted for the segregation of various transmission modes in families. The asthma prevalence in the interviewed index generation was 6.9% (95% confidence interval [CI]: 6.5 to 7.3), and in the parent generation was 6.1% (5.8 to 6.4). As with asthma prevalence, the risk of a subject having asthma if a parent had asthma also had a large geographic variation across the survey centers. The mean risk if a father had asthma was 2.9 (2.4 to 3.5), and If the mother had asthma was 3.2 (2.6 to 3.9). The risk increased to 7.0 (3.9 to 12.7) if both parents were affected. For developing extrinsic asthma, extrinsic asthma in any parent was a greater risk factor (4.9 [3.9 to 6.0]) than intrinsic asthma of the parent (1.5 [0.8 to 2.6]), and the risk for women was slightly higher than that for men (4.3 [3.3 to 5.5] versus 3.6 [2.6 to 5.0]). Applying different segregation models, only a model for a two-allele gene with a codominant inheritance could not be rejected, assuming a major gene with a population frequency of 24.2%. Further results make a multilocus/threshold model likely. In conclusion, a history of asthma in parents is a strong risk factor for asthma in the offspring. Under the assumptions of the applied segregation analysis, at least one major gene exists which could be a gene involved also in allergy. However, asthma is not fully described by a single-gene model. The risk for asthma varies within the European countries, and should be seen in the context of a complex genetic and environmental pathophysiology.