Some members of the diatom genus Pseudo-nitzschia produce the toxin domoic acid (DA), which through trophic transfer causes mass mortalities of wildlife, shellfish harvesting closures, and risks to human health. Nutrient and micronutrient limitation have been shown to regulate DA production. This study tested the hypothesis that changing partial pressure of CO 2 (pCO 2 ) can interact with nutrient limitation to help determine cellular DA levels, an environmentally relevant issue in light of current increases in atmospheric pCO 2 . Cultures of the toxic species Pseudo-nitzschia multiseries were incubated using semicontinuous methods under a matrix of three pCO 2 conditions: , 22 Pa (220 ppm), , 41 Pa (400 ppm), and , 74 Pa (730 ppm), and two phosphate concentrations: 20 mmol L 21 , P-replete; and 0.5 mmol L 21 , P-limited. DA production was regulated by both pCO 2 and phosphate availability. DA concentrations were 30-50 times higher in P-limited cultures compared to Preplete ones, at the same pCO 2 levels. Increasing CO 2 levels stimulated DA production under both nutrient conditions, but especially in P-limited cultures, where DA levels increased approximately four times over the pCO 2 range examined. Growth rates, primary productivity, photosynthesis vs. irradiance parameters, and cellular elemental ratios also responded interactively to the availability of both CO 2 and phosphate. Our results raise the possibility that growth rates and toxicity of the diatom Pseudo-nitzschia multiseries could increase substantially in the future high-CO 2 ocean, suggesting a potentially escalating negative effect of this harmful algal bloom species on the future marine environment.