Large cities in the United States face multiple challenges in meeting federal air quality standards. One difficulty arises from the uncertainties in evaluating traffic-related air pollution, especially the formation of secondary pollutants such as ozone and some particulate matter. Current air quality models are not well suited to evaluate the impact of a short-term traffic change on air quality. Using regional traffic and ambient air quality data from Southern California, we examine the impact of a two-day freeway closure on traffic and several criteria air pollutants (CO, NO2, O3, PM10, PM2.5). The results indicate that regional traffic decreased about 14% on average during the closure. Daily average PM2.5 levels decreased by about 32%, and daily 8 h maximum ozone levels decreased by about 16%. However, the daily 1 h maximum NO2 concentration was higher at some sites during the closure. Despite the mixed results with NO2, this study provides empirical evidence to support traffic reduction as an effective strategy to address chronic air pollution problems, especially with regard to ozone, in Southern California.