Elevated but variable levels of polychlorinated dibenzodioxins and polychlorinated dibenzofurans (PCDD/Fs) were observed in hardhead sea catfish (HH) and blue crabs (BCs), as well as in water and sediment, of the Houston Ship Channel system, Texas, USA. It is hypothesized that the variation was caused by the spatial variability of PCDD/F contamination, together with the natural mobility of organisms in satisfying prey, temperature, salinity, and reproductive requirements. Structural equation modeling was applied to explore the congener-specific relationships between PCDD/F levels in HH and BC tissues and independent predictors such as PCDD/F contamination levels, environmental factors such as salinity and temperature, temporal-spatial factors such as site depth and season, and biological factors such as length, weight, and lipid content. Contamination levels in both sediment and water were statistically significant predictors of the levels of less chlorinated congeners in both HH and BCs, with the standardized regression weight for sediment concentration roughly twice that for the water concentration. This implies that sediments are the dominant route for PCDDIF exposure and remediation efforts should focus on legacy sediment ontamination. Tissue lipid content was a significant predictor of tissue concentrations in HH but only to a lesser extent in BCs, perhaps due to their low lipid content. Site depth and seasonal factors also were significant predictors of tissue concentrations. For the highly chlorinated congeners, only a small fraction of the variance in tissue concentrations was explained by the independent predictors, possibly indicating that uptake and elimination kinetics, biotransformation processes, or both may be more important factors controlling the bioaccumulation of those congeners.