Two in-situ exposure studies were conducted with the federally-listed endangered Rio Grande silvery minnow (Hybognathus amarus). One-year-old adults were exposed in cages deployed at three sites in the Middle Rio Grande, N. Mex., for 4 days to assess survival and for 26 days to evaluate survival, growth, overall health, and whole-body elemental composition. The test sites were located on the Pueblo of Isleta in the (1) main channel of the Middle Rio Grande, (2) 240-Wasteway irrigation return drain, and (3) wetted instream habitat created below the outfall of the 240-Wasteway irrigation return drain. During the cage exposures, temperature, dissolved oxygen, pH, conductivity, and turbidity were monitored continuously (15-minute intervals) and common constituents, nutrients, carbons, metals, and pesticides were measured at discrete intervals. In both studies, there were statistical differences in several water-quality parameters among sites; and except for turbidity, these differences were small and were not considered to be biologically significant. The cages used in the 4-day exposure study were ineffective at preventing access to the fish by predators, and survival was highly variable (20 percent to 90 percent) across sites. In the 26-day chronic exposure study, weight and condition factor of caged-exposed fish at all sites were significantly lower than those at test initiation. After 26 days of exposure, there were no significant differences in survival, total length, weight, or condition factor of fish across sites, but absolute weight loss and relative reduction in condition factor were significantly greater in fish at the wetted instream habitat site compared to those at the Middle Rio Grande site. There were no statistical differences in health assessment indices, mesenteric fat indices, or prevalence of abnormalities in cage-exposed fish among sites. Cage-exposed fish had higher health assessment indices and prevalence of fin anomalies and a lower mesenteric fat indices compared to pre-exposed fish. Prevalence of macrophage aggregates in the kidney, liver, and spleen of caged-exposed fish was similar across sites and also was similar to those in pre-exposed fish. Absolute and relative weight loss and relative reduced condition factors were inversely correlated with water depth in the cages, which were the lowest at the WIH site.