Results from studies of traffic and childhood asthma have been inconsistent, but there has been little systematic evaluation of susceptible subgroups. In this study, we examined the relationship of local traffic-related exposure and asthma and wheeze in southern California school children (5-7 years of age). Lifetime history of doctor-diagnosed asthma and prevalent asthma and wheeze were evaluated by questionnaire. Parental history of asthma and child's history of allergic symptoms, sex, and early-life exposure (residence at the same home since 2 years of age) were examined as susceptibility factors. Residential exposure was assessed by proximity to a major road and by modeling exposure to local traffic-related pollutants. Residence within 75 m of a major road was associated with an increased risk of lifetime asthma [odds ratio (OR)=1.29; 95% confidence interval (CI), 1.01-1.86], prevalent asthma (OR=1.50; 95% CI, 1.16-1.95), and wheeze (OR=1.40; 95% CI, 1.09-1.78). Susceptibility increased in long-term residents with no parental history of asthma for lifetime asthma (OR=1.85; 95% CI, 1.11-3.09), prevalent asthma (OR=2.46; 95% CI, 0.48-4.09), and recent wheeze (OR=2.74; 95% CI, 1.71-4.39). The higher risk of asthma near a major road decreased to background rates at 150-200 m from the road. In children with a parental history of asthma and in children moving to the residence after 2 years of age, there was no increased risk associated with exposure. Effect of residential proximity to roadways was also larger in girls. A similar pattern of effects was observed with traffic-modeled exposure. These results indicate that residence near a major road is associated with asthma. The reason for larger effects in those with no parental history of asthma merits further investigation.