The treatment of olive oil mill effluents (OME), even when performed with the most appropriate technology (i.e. anaerobic digestion) meets great difficulties in reaching the depuration efficiencies required by national regulations all over the Mediterranean area. This paper was aimed at gaining better insight into the degradation of the main compounds contained in the OME; in particular, the interaction between the two successive stages occurring in the anaerobic digestion, the acidogenesis and the methanogenesis, was investigated. First of all, the best operating conditions were identified. Most of the lipids were degraded both in acidogenesis and methanogenesis tests. On the other hand, polyphenol-like substances were not degraded at all in acidogenic conditions, whereas they were partially removed in methanogenic conditions. A little methanogenic activity, established in acidogenic conditions because of the partial degradation of the chemical inhibitor, seems to be the key factor determining lipids degradation even in acidogenesis tests. Synthetic solutions were also tested. Oleic acid was degraded both in acidogenesis and methanogenesis tests, provided that an easily biodegradable substrate (glucose) was added to the solution. The presence of glucose was also required for the degradation of p-hydroxybenzoic acid in methanogenic conditions. This acid was not degraded at all in acidogenic conditions, thus confirming the results obtained in the tests on OME. Even if slightly lower, bioconversion yields of OME in acidogenesis are remarkably less sensitive to the effect of pH and substrate conditions than in methanogenesis. This result suggests that a two-phase anaerobic digestion might be adopted as a suitable process for optimizing OME degradation.