Nutrient and organic loading associated with escalating human activities increases biological oxygen demand from microbial decomposition. In the Neuse River estuary, North Carolina, recurrent nuisance algal blooms, bottom-water hypoxic events, and fish kills during summers of the 1990s suggest that uncapped nutrient loading may have increased the frequency, duration, and/or spatial scope of important biological effects of hypoxia during summer, when persistent water column stratification can occur and microbial metabolism is greatest. We test the hypothesis that the severity of benthic biological effects of hypoxia in this estuary has increased over a 30-year period of dramatic human population growth in eastern North Carolina by comparing survival over summer of the benthic bivalve Macoma spp. between historical (1968-1970) and recent (1997-1998) years. Macoma is a demonstrated indicator of oxygen availability, the benthic biomass dominant in the Neuse and other temperate estuaries and the major prey link to higher trophic levels. All three historical summers exhibited patterns of collapse in Macoma populations indistinguishable from the recent summer of severe hypoxia (1997) but distinct from the modest changes documented during the mildly hypoxic summer of 1998. The only Macoma to survive any severely hypoxic summer were those in shallows where oxygen could be renewed by surface mixing. Thus, the biological effects of hypoxia observed in the Neuse River estuary in the late 1990s appear no more severe than 30 years before. Historic rates of organic loading to the Neuse River estuary may have been sufficient to induce widespread and intense hypoxia beneath the surface mixed layer, implying that even if algal blooms are diminished through nutrient reductions, the severity of biological effects of bottom-water hypoxia may not change detectably.