Family history of asthma and allergies strongly influences asthma risk in children, but the association may differ for early-onset persistent, early-onset transient, and late-onset asthma. We analyzed the relation between family history and these types of asthma using cross-sectional data from a school-based study of 5,046 Southern California children. Parental and/or sibling history of asthma and allergy were generally more strongly associated with early-onset persistent asthma compared with early-onset transient or late-onset asthma. For children with two asthmatic parents relative to those with none, the prevalence ratio for early-onset persistent asthma was 12.1 [95% confidence interval (CI) = 7.91-18.7] compared with 7.51 (95% CI = 2.62-21.5) for early-onset transient asthma and 5.38 (95% CI = 3.40-8.50) for late-onset asthma. Maternal smoking in pregnancy was predominantly related to the risk of early-onset persistent asthma in the presence of parental history of allergy and asthma, and the joint effects were more than additive (interaction contrast ratio = 3.10, 95% CI = 1.45-4.75). Our results confirm earlier data that parental history of asthma and allergy is most strongly associated with early-onset persistent asthma and suggest that among genetically predisposed children, an early-life environmental exposure, maternal smoking during pregnancy, favors the development of early-onset asthma that persists into later early childhood.