ABSTRACT: BACKGROUND:Fine particulate matter (PM2.5) related mild inflammation, altered autonomic control of cardiovascular function, and changes to cell function have been observed in controlled human exposure studies. METHODS:To measure the systemic and cardiopulmonary impacts of low-level PM exposure, we exposed 20 healthy, young volunteers to PM2.5, in the form of concentrated ambient particles (mean: 37.8??g/m3, SD 6.5), and filtered air (mean: 2.1??g/m3, SD 2.6). In this double-blind, crossover study the exposure order was randomized. During the 4?h exposure, volunteers (7 females and 13 males) underwent light intensity exercise to regulate ventilation rate. We measured pulmonary, cardiac, and hematologic end points before exposure, 1?h after exposure, and again 20?h after exposure. RESULTS:Low-level PM2.5 resulted in both pulmonary and extra-pulmonary changes characterized by alterations in systematic inflammation markers, cardiac repolarization, and decreased pulmonary function. A mean increase in PM2.5 concentration (37.8??g/m3) significantly increased serum amyloid A (SAA), C-reactive protein (CRP), soluble intercellular adhesion molecule-1 (sICAM-1), and soluble vascular cell adhesion molecule-1 (sVCAM-1), 1?h after exposure by 8.7, 9.1, 10.7, and 6.6%, respectively, relative to the filtered air control. SAA remained significantly elevated (34.6%) 20?h after PM2.5 exposure which was accompanied by a 5.7% decrease in percent neutrophils. Decreased pulmonary function was observed 1?h after exposure through a 0.8 and 1.2% decrease in forced expiratory volume in 1?s (FEV1) and FEV1/ forced vital capacity (FEV1/FVC) respectively. Additionally, sex specific changes were observed in repolarization outcomes following PM2.5 exposure. In males, P-wave and QRS complex were increased by 15.4 and 5.4% 1?h after exposure. CONCLUSIONS:This study is the first controlled human exposure study to demonstrate biological effects in response to exposure to concentrated ambient air PM2.5 particles at levels near the PM2.5 US NAAQS standard. CLINICAL TRIAL REGISTRATION INFORMATION:clinicaltrials.gov ; Identifier: NCT03232086 . The study was registered retrospectively on July 25, 2017, prior to final data collection on October 25, 2017 and data analysis.