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Several lines of evidence from the Regional Monitoring Program and other studies have suggested that sediment grain size characteristics influence amphipod (Eohaustorius estuarius) survival in 10 day toxicity tests. Two workshops were convened to address the influence of non-contaminant factors on amphipod toxicity tests, and the current project was prioritized based on the recommendations of experts participating in these workshops. The study was designed to investigate the effects of kaolin clay on amphipod survival since this is the dominant clay type in Francisco Estuary sediments. In these experiments reference sand was spiked with increasing concentrations of kaolin to determine whether there was a dose-based relationship between amphipod mortality and increasing concentrations of this type of clay. Wild-caught E. estuarius were collected from Beaver Creek Beach (Oregon) and supplied by Northwest Aquatic Sciences. The initial experiment did not demonstrate a dose-response relationship: E. estuarius survival in all concentrations from 10% to 100% kaolin was lower than in the sand control, and survival in the clay spiked sand was also highly variable. This experiment exposed a mixture of amphipod size classes representative of those typically provided by the amphipod supplier. Reasoning that variable response to clay was related to variable tolerances by the different amphipod size classes, a follow-up experiment was conducted to investigate this relationship. Amphipods were separated into small, medium and large size classes and these were exposed to 100% kaolin. These results showed survival in 100% clay was 86%, 82% and 66% by small, medium and large amphipods, respectively. To further investigate size-related responses to clay, small, medium and large amphipods were exposed to concentrations of sand spiked with clay from 0 to 100%. The results of this experiment showed that smaller amphipods tolerated high clay concentrations better than larger animals, but there was not a strict monotonic dose-response relationship. Conclusions based on this experiment were constrained by an inability to sort amphipods into three distinct size classes, because there were not enough of the largest animals present at the Oregon collection site. In addition, grain size analysis of the sand spiked clay suggested that the clay tended to flocculate in the treatments above 70% kaolin. This experiment was repeated when three distinct size classes were present in December 2014. The results of this experiment also showed that smaller amphipods tolerated high kaolin better than larger amphipods. As in the previous experiment, there was not a monotonic response to clay, especially at the higher kaolin concentrations, and the grain size analysis also showed flocculation occurred in the highest clay treatments. Despite these inconsistencies, the results of this experiment suggest that tolerance of E. estuarius to clay varies with amphipod size. Average survival was 81%, 79%, and 65% for small, medium and large amphipods, respectively in concentrations > 50% clay. Possible mechanisms for size specific clay effects on this amphipod species include lower survival related to reduced energy reserves in larger animals, inhibition of gill function, and inhibition of feeding and locomotion through clogging of amphipod setae. The results suggest that use of smaller amphipods in routine monitoring of high clay sediments will reduce the influence of this factor on test results. Additional experiments with high clay reference site sediments from San Francisco Bay are recommended to confirm the size related response with field sediments.