Domoic acid is a potent neurotoxin produced by certain marine microalgae that can accumulate in the foodweb, posing a health threat to human seafood consumers and wildlife in coastal regions worldwide. Evidence of climatic regulation of domoic acid in shellfish over the past 20 y in the Northern California Current regime is shown. The timing of elevated domoic acid is strongly related to warm phases of the Pacific Decadal Oscillation and the Oceanic Niño Index, an indicator of El Niño events. Ocean conditions in the northeast Pacific that are associated with warm phases of these indices, including changes in prevailing currents and advection of anomalously warm water masses onto the continental shelf, are hypothesized to contribute to increases in this toxin. We present an applied domoic acid risk assessment model for the US West Coast based on combined climatic and local variables. Evidence of regional-to basin-scale controls on domoic acid has not previously been presented. Our findings have implications in coastal zones worldwide that are affected by this toxin and are particularly relevant given the increased frequency of anomalously warm ocean conditions.T he Pacific Decadal Oscillation (PDO) and El Niño Southern Oscillation (ENSO) are recurring patterns of climate variability centered over the northeastern (NE) and equatorial Pacific, respectively, that fluctuate at scales of years (ENSO) to decades (PDO) (1, 2). Distinct, yet also related, these patterns can amplify or dampen each other through atmospheric teleconnection (1, 3). In the NE Pacific, they induce similar spatial patterns of sea surface temperature anomalies during positive (warm) and negative (cool) phases (4). Low-frequency physical variability attributed to the PDO and ENSO modulates large shifts in NE Pacific water temperature, ocean currents, and foodweb dynamics that can persist for months to years (2,5,6). Shifts in NE Pacific plankton communities occur as well (7-12); however, climate impacts on phytoplankton ecology in this region are relatively underexplored, largely due to a lack of phytoplankton data at sufficient scales.Decadal, regional-scale monitoring of domoic acid (DA) in shellfish can be used to investigate climate-scale impacts on phytoplankton ecology. The neurotoxin DA is produced by some species of the diatom genus Pseudo-nitzschia. It enters secondary trophic levels when suspension feeders such as shellfish and anchovies ingest toxic Pseudo-nitzschia cells. Consumption of these organisms by humans can lead to a serious neurological disorder named Domoic Acid Poisoning (DAP), also termed Amnesic Shellfish Poisoning. DAP symptoms range from gastrointestinal disturbance to seizures, memory loss, or, rarely, death (13,14).DA was first identified as a public health threat in 1987 (15). Toxin-producing Pseudo-nitzschia spp. and DA have since been identified worldwide with the greatest prevalence in, and most deleterious impacts on, productive eastern boundary upwelling systems (16). Laboratory experiments have found multiple ...