E-cigarettes are generally thought of as a safer smoking alternative to traditional cigarettes. However, little is known about the effects of e-cigarette liquids (e-liquids) on the lung. Since over 7,000 unique flavors have been identified for purchase in the USA, our goal was to conduct a screen that would test whether different flavored e-liquids exhibited different toxicant profiles. We tested the effects of 13 different flavored e-liquids (with nicotine and propylene glycol/vegetable glycerin (PG/VG) serving as controls) on a lung epithelial cell line (CALU3). Using the MTT assay as an indicator of cell proliferation/viability, we demonstrated a dose-dependent decrease of MTT metabolism by all flavors tested. However, a group of 4 flavors consistently showed significantly greater toxicity compared to the PG/VG control, indicating the potential for some flavors to elicit more harmful effects than others. We also tested the aerosolized 'vapor' from select e-liquids on cells and found similar dose-dependent trends, suggesting that direct e-liquid exposures are a justifiable first-pass screening approach for determining relative e-liquid toxicity. We then identified individual chemical constituents for all 13 flavors using gas chromatography-mass spectrometry. These data revealed that beyond nicotine and PG/VG, the 13 flavored e-liquids have diverse chemical constituents. Since all of the flavors exhibited some degree of toxicity and a diverse array of chemical constituents with little inhalation toxicity available, we conclude that flavored e-liquids should be extensively tested on a case-by-case basis to determine the potential for toxicity in the lung and elsewhere.