Populations of white sturgeon (Acipenser transmontanus) are in decline in North America. This is attributed, primarily, to poor recruitment, and white sturgeon are listed as threatened or endangered in several parts of British Columbia, Canada, and the United States. In the Columbia River, effects of metals have been hypothesized as possible contributing factors. Previous work has demonstrated that early life stage white sturgeon are particularly sensitive to certain metals, and concerns over the level of protectiveness of water quality standards are justified. Here we report results from acute (96-h) toxicity tests for copper (Cu), cadmium (Cd), zinc (Zn), and lead (Pb) from parallel studies that were conducted in laboratory water and in the field with Columbia River water. Water effect ratios (WERs) and sensitivity parameters (i.e., median lethal accumulations, or LA50s) were calculated to assess relative bioavailability of these metals in Columbia River water compared to laboratory water, and to elucidate possible differences in sensitivity of early life stage white sturgeon to the same concentrations of metals when tested in the different water sources. For Cu and Pb, white sturgeon toxicity tests were initiated at two life stages, 8 and 40 days post-hatch (dph), and median lethal concentrations (LC50s) ranged between 9-25 μg Cu/L and 177-1,556 μg Pb/L. LC50s for 8 dph white sturgeon exposed to Cd in laboratory water and river water were 14.5 and 72 μg/L, respectively. Exposure of 8 dph white sturgeon to Zn in laboratory and river water resulted in LC50s of 150 and 625 μg/L, respectively. Threshold concentrations were consistently less in laboratory water compared with river water, and as a result, WERs were greater than 1 in all cases. In addition, LA50s were consistently greater in river water exposures compared with laboratory exposures in all paired tests. These results, in combination with results from the biotic ligand model, suggest that the observed differences in toxicity between river water exposures and laboratory water exposures were not entirely due to differences in water quality and metal bioavailability but rather in combination with differences in fish sensitivity. It is hypothesized that differences in concentrations of calcium in the different water sources might have resulted in differences in acquired sensitivity of sturgeon to metals. Canadian water quality guidelines, US national criteria for the protection of aquatic life, and water quality criteria for the state of Washington were less than LC50 values for all metals and life stages tested in laboratory and Columbia River water. With the exception, however, that 40 dph white sturgeon exposed to Cu in laboratory water resulted in threshold values that bordered US national criteria and criteria for the state of Washington.