We assessed the effects of fish predation on zebra mussels (Dreissena polymorpha) in Navigation Pool 8 of the Upper Mississippi River from 13 May to 5 October, 1998. Concrete-block samplers were deployed at 18 randomly chosen sites in the main-channel border, with 6 sites in the upper, middle, and lower segments of the pool. Two blocks, 1 of which was enclosed in a cage to exclude large predatory fishes, were deployed at each site. After 145 d, blocks were retrieved from 12 of the 18 sites, and zebra mussels were found on all blocks. Densities of zebra mussels were higher on caged blocks than uncaged blocks, and the magnitudes of the differences varied spatially. Mean mussel densities on uncaged blocks were reduced by 66%, 86%, and 20% compared to caged blocks in the upper, middle, and lower pool segments, respectively, over the 145-d interval. Mean daily instantaneous zebra mussel mortality rates from large predators ranged from 0.0016 to 0.0138. Similarly, biomass of zebra mussels was higher on caged than uncaged blocks. Mean mussel biomass on uncaged blocks was reduced by 64% pool-wide, relative to biomass on caged blocks. Zebra mussels were consumed by at least 6 fish taxa including redhorse suckers (Moxostoma spp.), common carp (Cyprinus carpio), bluegill (Lepomis macrochirus), quillback carpsucker (Carpiodes cyprinus), flathead catfish (Pylodictis olivaris), and freshwater drum (Aplodinotus grunniens). Fish predation had an important moderating effect on zebra mussel demography in Pool 8.