Vranjic Basin, in the eastern part of KastelaBay (middle Adriatic Sea), received municipal wastewater until offshore submarine outfalls were finished in November 2004. To identify the responses of the microbial community to changes in the trophic status of the marine environment, two 4-year periods were compared: a eutrophic period (2001-2004) when the sewage waters entered the Basin and an oligotrophic period (2005-2008) after the outfalls were completed. The switch from eutrophic to oligotrophic conditions was accompanied by decreases in bacterial abundance, bacterial production and chlorophyll a, and increase in heterotrophic nanoflagellate (HNF) abundance and bacterial specific growth rate. Qualitative changes in the phytoplankton community manifested through dramatically decreased abundance of the diatom species Skeletonema costatum and Euglenophyta Eutreptiella spp. during the oligotrophic period. Furthermore, the percent contribution of pico-nano phytoplankton chlorophyll to total chlorophyll increased from less than 40% during the eutrophic period to more than 60% during the oligotrophic period. Changes in seasonal patterns of phytoplankton, bacteria and HNF abundance were also observed, with summer maxima during the eutrophic period and spring and autumn maxima during the oligotrophic period. Significant changes in the microbial food web were also identified. During eutrophic conditions, bacteria were dominantly under the phytoplankton-mediated bottom-up control whereas HNF were dominantly controlled by ciliate grazing (top-down control). In contrast, during the oligotrophic period, predominantly top-down control of bacteria by strong HNF grazing was observed. At the same time, HNF were spared from strong ciliate predation pressure because the ciliates apparently switched their dominant prey from HNF to the pico-nano phytoplankton fraction during that period.