The developed world has invested billions of dollars in waste treatment since the 1970s; however, changes in ecological or biological responses are rarely associated with reductions in metal pollutants. Here we present a novel, 23-yr time series of environmental change from a San Francisco Bay mudflat located 1 km from the discharge of a suburban domestic sewage treatment plant. Samples of surface sediment, the bioindicator Macoma balthica, and metals loading data were used to establish links between discharge, bioaccumulation, and effects. Mean annual Ag concentrations in M. balthica were 106 μg/g in 1978 and 3.67 μg/g in 1998. Concentrations of Cu declined from 287 μg/g in 1980 to a minimum of 24 μg/g in 1991. Declining Cu bioaccumulation was strongly correlated with decreasing Cu loads from the plant between 1977 and 1998. Relationships with bioaccumulation and total annual precipitation suggested that inputs from nonpoint sources were most important in controlling Zn bioavailability during the same period. Ecoepidemiological criteria were used to associate failed gamete production in M. balthica to a metals-enriched environment. Reproduction persistently failed between the mid-1970s and mid-1980s; it recovered after metal contamination declined. Other potential environmental causes such as food availability, sediment chemistry, or seasonal salinity fluctuations were not related to the timing of the change in reproductive capability. The results establish an associative link, suggesting that it is important to further investigate the chemical interference of Cu and/or Ag with invertebrate reproduction at relatively moderate levels of environmental contamination.