Waterpipe (WP) tobacco smoking remains an important public health concern among young adults in the US, with 1 in 8 reporting past year use. Like cigarettes, WP smoking can lead to cancer, impaired pulmonary function, and heart disease due to toxicants such as carcinogenic polycyclic aromatic hydrocarbons (PAHs), volatile aldehydes (VAs), and carbon monoxide (CO). The FDA has taken steps to regulate WP products, but the complex landscape of WP configurations, including diverse heat sources and varying device sizes, presents regulatory challenges. Adding to these concerns is the marketing of so-called WP “harm reduction” products like electrical heaters and “mini hookahs” that lack supportive data and may perpetuate WP use. Our preliminary findings indicate that electrical heaters can reduce CO and PAH yields but may increase VA emissions and total smoke inhaled. Additionally, larger WPs are associated with increased CO exposure and higher harm perceptions, while smaller WPs result in higher nicotine exposure. These findings underscore the need for comprehensive research on the impact of WP size and heat source on toxicant exposure, smoking behavior, and abuse liability. This R21 project aims to elucidate the effects of WP size and heat source on toxicant exposure, smoking behavior, and abuse liability through a 2x2 crossover study involving 60 young adult WP smokers (aged 21-39 years). Participants will undergo four 45-minute WP smoking sessions, each with a different WP size and heat source configuration (small vs. large WP, charcoal vs. electrical heater). We will measure puff topography, saliva nicotine, exhaled CO, subjective experiences, and abuse liability pre- and post-smoking. We hypothesize that smoking a configuration of large WP size with a charcoal heat source will result in higher levels of toxicant exposure, increased puffing behavior, and greater abuse liability while smoking a configuration of small WP size with an electrical heat source. Manipulatin