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As seawater acidifies, the rate of iron (Fe) uptake by the nitrogen (N2)-fixing cyanobacterium Trichodesmium declines in an EDTA-buffered medium. The slower Fe uptake rate at low pH results from changes in Fe chemistry and not from a physiological response of the organism caused by decreasing pH. Contrary to previous observations with an artificial media, increasing pCO2 causes a decrease in the rates of N2 fixation and growth in Fe-limited Trichodesmium grown in natural seawaters. This result was obtained even though the bioavailability of Fe was maintained constant by increasing the total Fe concentration at low pH.