The N-2-hydroxyethylpiperazine-N′-2-ethanesulfonic acid (HEPES) is extensively used as pH buffer in culture media for testing chemicals. However, this study demonstrates that 0.01 M HEPES significantly reduces the rate of Cu, Pb, and Cd binding to Porphyra spp. and Enteromorpha spp. marine macroalgae. The HEPES also decreased the accumulation of Cu, Pb, and Cd but not Hg by these macroalgae. Both the extracellular adsorption and the intracellular uptake of the metals were influenced by HEPES to a similar extent. The HEPES also promoted the release of exudates by the algae, and these exudates form very stable complexes with Cu (and probably with other trace metal ions). The HEPES interference varied with the nature of the metal, the macroalga, and the season. The presence of 0.01 M HEPES in seawater cultures of the Emiliania huxleyi (a microalga) also interfered with E. huxleyi growth, liberation of Cu-complexing organic ligands, and Cu uptake. The HEPES, which displays surface activity, may facilitate the binding of metals to the algae for an initial exposure period. The metal taken up appears to stimulate the liberation of exudates that subsequently control the bioavailability of the metals and therefore metal uptake. Because HEPES can control the uptake of trace metals by algae and the production of organic ligands, the results obtained in cultures containing the HEPES pH buffer can be influenced by this component of the media.