We estimated the loss of juvenile salmonids Oncorhynchus spp. to predation by northern squawfish Ptychocheilus oregonensis, walleyes Stizostedion vitreum, and smallmouth bass Micropterus dolomieu in John Day Reservoir during 1983–1986. Our estimates were based on measures of daily prey consumption, predator numbers, and numbers of juvenile salmonids entering the reservoir during the April–August period of migration. We estimated the mean annual loss was 2.7 million juvenile salmonids (95% confidence interval, 1.9–3.3 million). Northern squawfish were responsible for 78% of the total loss; walleyes accounted for 13% and smallmouth bass for 9%. Twenty-one percent of the loss occurred in a small area immediately below McNary Dam at the head of John Day Reservoir. We estimated that the three predator species consumed 14% (95% confidence interval, 9–19%) of all juvenile salmonids that entered the reservoir. Mortality changed by month and increased late in the migration season. Monthly mortality estimates ranged from 7% in June to 61% in August. Mortality from predation was highest for chinook salmon O. tshawytscha, which migrated in July and August. Despite uncertainties in the estimates, it is clear that predation by resident fish predators can easily account for previously unexplained mortality of out-migrating juvenile salmonids. Alteration of the Columbia River by dams and a decline in the number of salmonids could have increased the fraction of mortality caused by predation over what it was in the past.