A real-world assessment of the source-to-receptor pathways for ambient particulate matter (PM), as opposed to in a laboratory environment, was crucial for gaining a better understanding of the types of particles to which people are actually exposed in their daily lives, and of the human-health risks for source-specific PM. However, obtaining scientific evidence linking specific source emissions to health responses was not an easy task; ambient PM possesses diverse chemical, physical and thermodynamic properties, and is subjected to numerous complex atmospheric processes in which source type, source strength, sinks, and meteorology interact continuously. Our collaborative PM health research studies utilized an integrated approach that employs detailed characterization of ambient PM concurrent with inhalation toxicology studies using animal models and concentrated fine air particulates (CAPs). Ambient PM2.5 (PM less than 2.5 microm in mean aerodynamic diameter) was concentrated with a Harvard fine particle concentrator housed in AirCARE1, a unique mobile air research laboratory which enables inhalation exposure studies in real-world settings. This paper discusses the importance of comprehensive characterization of ambient PM2.5, CAPs and their sources, and the associated challenges. In a southwest Detroit community where the pediatric asthma rate is about three times the national average, a detailed assessment was performed including: characterization of ambient PM2.5 and CAPs; identification of major emission sources of PM2.5; and quantification of trace elements in lung tissues of laboratory rats that were exposed to CAPs, all in an effort to define source-receptor pathways for ambient PM2.5. Our findings to date constitute evidence of the retention of ambient urban particulates from local combustion sources within animal tissues from short-term exposures, and possible associations between the observed health effects and source-specific PM2.5. However, a complete understanding of the effects of complex mixtures of air pollutants and their toxicological impacts still faces many challenges.