We examined the feasibility of stimulating methanogenic crude oil biodegradation through the combined supply of CO2 and protein-rich matter in anaerobic microcosms, without the external supply of H-2, and using formation waters and crude oil collected from the Stillwater and Cushing oil fields of Oklahoma, USA. We found that, depending on the chemical and microbiological composition of the formation water, protein-rich matter can stimulate methanogenic crude oil biodegradation if supplied along with CO2. For the low salinity (116, 714 mg/L) Stillwater oil field formation water, during the early stages of the stimulation process, CH4 was produced by the microbiological reduction of the supplied CO2 with H-2 produced from the syntrophic/fermentative biodegradation of the supplied protein-rich matter. As indicated by 16S rRNA gene community analysis, this resulted in a syntrophic enrichment of a methanogenic crude oil-degrading microbial community and led to> 42% crude oil biodegradation with the concurrent production of CH4 after 100 days of incubation at 50 degrees C. For the high salinity (176,665 mg/L) Cushing oil field formation water, although H-2 was produced, enrichment of a methanogenic crude oil-degrading microbial community-and thus CH4 production-was not possible. We tested two types of protein-rich matter (yeast extract and isolated soy protein) and found that isolated soy protein can be used as a substitute for yeast extract in field-scale applications. These findings have large implications toward the coupling of geological CO2 storage and microbial enhanced oil recovery in depleted oil reservoirs.