Many epidemiologic studies provide evidence of an association between daily counts of mortality and ambient particulate matter<10 microm in diameter (PM10). Relatively few studies, however, have investigated the relationship of mortality with fine particles [PM<2.5 microm in diameter (PM2.5)], especially in a multicity setting. We examined associations between PM2.5 and daily mortality in nine heavily populated California counties using data from 1999 through 2002. We considered daily counts of all-cause mortality and several cause-specific subcategories (respiratory, cardiovascular, ischemic heart disease, and diabetes). We also examined these associations among several subpopulations, including the elderly (>65 years of age), males, females, non-high school graduates, whites, and Hispanics. We used Poisson multiple regression models incorporating natural or penalized splines to control for covariates that could affect daily counts of mortality, including time, seasonality, temperature, humidity, and day of the week. We used meta-analyses using random-effects models to pool the observations in all nine counties. The analysis revealed associations of PM2.5 levels with several mortality categories. Specifically, a 10-microg/m3 change in 2-day average PM2.5 concentration corresponded to a 0.6% (95% confidence interval, 0.2-1.0%) increase in all-cause mortality, with similar or greater effect estimates for several other subpopulations and mortality subcategories, including respiratory disease, cardiovascular disease, diabetes, age>65 years, females, deaths out of the hospital, and non-high school graduates. Results were generally insensitive to model specification and the type of spline model used. This analysis adds to the growing body of evidence linking PM2.5 with daily mortality.