BACKGROUND: Daily increases in ambient ozone have been associated with increased mortality. However, little is known about which subpopulations are more susceptible to death related to ozone. METHODS: We conducted a case-only study in 48 US cities to identify subpopulations particularly vulnerable to ozone air pollution. Mortality and ozone data were obtained for the period 1989-2000 (May through September of each year) for 2,729,640 decedents. For each potential effect modifier, we fitted city-specific logistic regression models and pooled the results across all cities. Additionally, we examined differences in susceptibility factors according to several city characteristics using a meta-regression. RESULTS: For each 10 ppb increase in ozone (average of lags 0 to 2), people aged > or Euro Surveillance (Bulletin Europeen Sur Les Maladies Transmissibles; European Communicable Disease Bulletin)65 years had a 1.10% (95% confidence interval Euro Surveillance (Bulletin Europeen Sur Les Maladies Transmissibles; European Communicable Disease Bulletin) 0.44% to 1.77%) additional increase in mortality (compared with younger ages). Other groups that were particularly susceptible were black people (additional 0.53% [0.19% to 0.87%]), women (additional 0.58% [0.18% to 0.98%]), and those with atrial fibrillation (additional 1.66% [0.03% to 3.32%]). Susceptibility factors had a larger effect in cities with lower ozone levels. For instance, the additional increase in ozone-related mortality for the elderly was 1.48% (0.81% to 2.15%) in a city with a mean ozone level of 42 ppb versus 0.45% (-0.27% to 1.19%) in a city with a level of 51 ppb. CONCLUSIONS: We confirmed the susceptibility of the elderly to die of ambient ozone and identified other vulnerable subpopulations including women, blacks, and those with atrial fibrillation. Differences in vulnerability were particularly marked in cities with lower ozone concentrations.