This paper concerns the current debate as to whether oceans are heterotrophic or autotrophic environments. Microbes are responsible for the assimilation and remineralization of CO2 in the sea and microbial processes are involved in the Earth climatic change. The variability of microbial biomass and activities were studied in the Mediterranean Sea which represents a suitable basin for mapping the trophic regimes by the study of biogeochemical processes. The surveys were carried out in the epi-, meso- and bathy-pelagic zones of the Central Mediterranean Sea from 1996 to 2002. Bacterial abundance, leucine aminopeptidase (LAP) and β-glucosidase (β-GLU) activities, bacterial carbon production (BCP), community respiration (R) and primary production (PP) were the main parameters investigated.Biomass and activities seasonally varied in epipelagic and, to some extent, in meso- and bathy-pelagic layers too and several trophic ratios were determined, showing different scenarios in the different areas and seasons. In the euphotic layer, bacterial growth efficiency (BGE) widely ranged between 4% and 50% showing a decreasing trend from estuaries towards pelagic areas in alignment with the trophic gradient from the Northern Adriatic to the Ionian Sea. However, BGE did not correlate to PP and temperature.The Central Mediterranean Sea showed different trophic regimes in the examined areas and seasons. In the Northern Adriatic Sea in winter, the trophic balance appeared to move towards autotrophy and a positive C budget resulted. An opposite scenario happened in summer when the trophic balance moved to heterotrophy and a negative C budget occurred. In the Ionian Sea, the overall balance turned always towards remineralization. However, on annual time scale, the Central Mediterranean Sea seems to show a tendency towards a heterotrophic system.