Populations of freshwater mussels (Unionoida) are declining or disappearing from many waters around the world. In many declining populations, recruitment fails before adult mortality occurs, resulting in relict populations that can persist for decades. We tested whether recruitment failure in populations of the freshwater mussel Elliptio complanata was associated with invasion of nonnative crayfish, loss of a primary fish host (American eel Anguilla rostrata), excessive inputs of fine sediments, or unfavorable interstitial water chemistry (too little dissolved oxygen or too much un-ionized ammonia). We sampled mussel populations, crayfish populations, and environmental conditions at 14 sites on wadeable streams in southeastern New York. Five of the mussel populations had little or no recent recruitment. We found no association between recruitment failure and crayfish, American eels, fine sediments, or interstitial dissolved oxygen. In contrast, recruitment failure was strongly associated with high concentrations (>0.2 microg N/L) of un-ionized ammonia. This threshold is much lower than thresholds for acute ammonia toxicity identified in laboratory studies. We suggest that excessive concentrations of interstitial un-ionized ammonia may be responsible for widespread declines of freshwater mussel populations, especially in agricultural areas.