Marine prokaryotes play a key role in cycling of organic matter and nutrients in the ocean. Using a unique dataset (>14,500 samples), we applied a space-for-time substitution analysis to assess the temperature dependence of prokaryotic heterotrophic production (PHP) in epi- (0-200 m), meso- (201-1000 m) and bathypelagic waters (1001-4000 m) of the global ocean. Here, we show that the temperature dependence of PHP is fundamentally different between these major oceanic depth layers, with an estimated ecosystem-level activation energy (E-a) of 36 +/- 7 kJ mol(-1) for the epipelagic, 72 +/- 15 kJ mol(-1) for the mesopelagic and 274 +/- 65 kJ mol(-1) for the bathypelagic realm. We suggest that the increasing temperature dependence with depth is related to the parallel vertical gradient in the proportion of recalcitrant organic compounds. These E-a predict an increased PHP of about 5, 12, and 55% in the epi-, meso-, and bathypelagic ocean, respectively, in response to a water temperature increase by 1 degrees C. Hence, there is indication that a major thus far underestimated feedback mechanism exists between future bathypelagic ocean warming and heterotrophic prokaryotic activity.