Volatile fatty acids (VFAs) are key intermediates in anaerobic digestion. Enriched acetogenic and methanogenic cultures were used for syntrophic anaerobic digestion of VFAs in a high-load continuous reactor fed with acetic (HAc), propionic (HPr) and butyric (HBu) acids at maximum concentrations of 5, 3 and 4 g/L, respectively. Interactive effects of HPr, HBu and HAc were analyzed. Furthermore, hydraulic retention time (HRT) and methanogen to acetogen population ratio (M/A) were investigated as key microbiological and operating variables of VFA anaerobic degradations. Optimum conditions were found to be HPr = 1125.0 mg/L, HBu = 1833.4 mg/L, HAc = 1727.4 mg/L, HRT = 21 h and M/A = 2.5 (corresponding to maximum VFA removal and biogas production rate (BPR)). Results of verification experiments and predicted values from fitted correlations were in close agreement at 95% confidence interval. HRT and M/A had positive effects on VFA removal and BPR. M/A was the most important factor that affected BPR. All VFAs inhibited VFA removals. (C) 2010 Elsevier Ltd. All rights reserved.