In the tidal creeks of North Inlet, a high salinity salt marsh estuary near Georgetown, South Carolina, USA, the Eastern oyster Crassostrea virginica is an abundant component of the benthic macrofauna that exerts controls on microbial communities by its grazing and nutrient regenerative activities. The effects of oyster activity on North Inlet microbial food web structure were studied using:(1) water samples collected from tidal creeks with oyster reefs versus tidal creeks without oyster reefs (removed as part of a large-scale field manipulation study); and (2) flow-through flumes. In pair-wise comparisons of creeks with similar hydrography and morphology, the only microbial group found to vary significantly with the presence of oyster reefs was the phototrophic nanoflagellates (pflags), which were 1.25-to 2.25-fold less abundant in creeks with oyster reefs during the summer phytoplankton bloom. Because heterotrophic nanoflagellates (hflags) did not vary in these same comparisons, we hypothesized that preferential feeding for pflags by oysters was responsible for the reduction in pflag abundance. The hypothesis was tested during March and July 1999 using flumes with flowing creek water containing either live oysters or dead oyster shells. Significant reductions in pflags and some types of diatoms were measured in the outflow from live oysters, but oyster effects on other microbial components (hflags, cyanobacteria, and heterotrophic bacterioplankton) were not evident. The flume study demonstrated preferential feeding by oysters on pflags using naturally occurring microbial assemblages. The differences in pflag abundance in creeks with oyster reefs versus creeks without oyster reefs suggests that this grazing activity can affect the structure of natural microbial communities.