Health risk assessments of particulate matter less than 2.5 μm in diameter (PM(2.5)) often assume that all constituents of PM(2.5) are equally toxic. While investigators in previous epidemiologic studies have evaluated health risks from various PM(2.5) constituents, few have conducted the analyses needed to directly inform risk assessments. In this study, the authors performed a literature review and conducted a multisite time-series analysis of hospital admissions and exposure to PM(2.5) constituents (elemental carbon, organic carbon matter, sulfate, and nitrate) in a population of 12 million US Medicare enrollees for the period 2000-2008. The literature review illustrated a general lack of multiconstituent models or insight about probabilities of differential impacts per unit of concentration change. Consistent with previous results, the multisite time-series analysis found statistically significant associations between short-term changes in elemental carbon and cardiovascular hospital admissions. Posterior probabilities from multiconstituent models provided evidence that some individual constituents were more toxic than others, and posterior parameter estimates coupled with correlations among these estimates provided necessary information for risk assessment. Ratios of constituent toxicities, commonly used in risk assessment to describe differential toxicity, were extremely uncertain for all comparisons. These analyses emphasize the subtlety of the statistical techniques and epidemiologic studies necessary to inform risk assessments of particle constituents.