Specific environmental cues responsible for stimulating the accumulation of domoic acid (DA) in Pseudo-nitzschia spp. are poorly defined, although some evidence indicates that production of DA can be stimulated by exposure of cells to elevated metal (Li) concentrations (Subba Rao et al. 1998, P.S.Z.N. Mar. Ecol. 19:31). Other algal species have been observed to produce the amino proline (an structural analogue of DA) in response to elevated copper (Cu) concentrations suggesting a potential complexation strategy, since proline exhibits chemical characteristics found in many unidentate ligands. As part of our ongoing studies investigating the interrelationship of proline and DA metabolism, we evaluated the response in DA pools during exposure of several Pseudo-nitzschia species to varying total Cu availability, ranging from limitation to toxicity. Copper enrichment experiments revealed that P. multiseries strain MU5 increased cell yield by ca. 2-fold when cultured in elevated Cu conditions (0.16 to 16 µM Cu+2) compared to standard f/2 (0.03 µM Cu+2); P. australis strain AU43 did not exhibit this trend. In both species, the production of DA was not stimulated by exposure to elevated Cu concentrations. However, the difference in the growth repsonse between the two species was associated with MU5 maintaining a 100-fold higher DA content, relative to the total amino acid pool, compared to AU43. As domoic acid is comprised of three carboxylic acid groups, a prolyl ring conjugated to an isoprenoid side chain, it is predicted that DA will exhibit enhanced chelation capacity for copper (and other metals) relative to proline, however, stability constants with respect to copper have not yet been measured for this compound. Flow injection analysis with chemiluminescent detection will be used to measure the affinity constants for DA-Cu interactions. The potential role of DA in intracelluar copper homeostasis in Pseudo- nitzschia spp. will be discussed.