The optimization of total solids in the feed (%TS) and alkalinity ratio (gamma) for H(2) production from organic solid wastes under thermophilic regime was carried out using response surface methodology based on a central composite design. The total solids levels were 20.9, 23.0, 28.0, 33.0 and 35.1% whereas the levels of alkalinity ratio (defined as g phosphate alkalinity/g dry substrate) were 0.15, 0.20, 0.30, 0.41 and 0.45. High levels of TS and gamma affected in a negative way the H,. productivity and yield; both response variables significantly increased upon decreasing the TS content and alkalinity ratio. The highest H(2) productivity and yield were 463.7 N mL/kg-d and S4.8 N mL/g VS(rem), respectively, predicted at 20.9% TS and alkalinity ratio 0.25 (0.11 gCaCO(3)/g dry substrate). The alkalinity requirements for hydrogenogenic processes were lower than those reported for methanogenic processes (0.11 vs. 0.30 g CaCO(3)/g COD). Adequate alkalinity ratio was necessary to maintain optimal biological activity for hydrogen production; however, excessive alkalinity negatively affected process performance probably due to an increase of osmotic pressure. interestingly, reactor pH depended only on the alkalinity ratio, thus the buffer capacity was able to maintain a constant pH independently of TS levels. At gamma = OAS-0.30 the pHs were in the range 5.56-5.95, which corresponded to the highest hydrogen productivities and yields. Finally, the highest metabolite accumulation corresponded with the highest removal efficiencies but not with high H(2) productivities and yields. Therefore, it seems that organic matter removal was channeled toward solvent generation instead of hydrogen production at high TS and gamma levels. This is the first study that shows the requirements of alkalinity in solid substrate fermentation conditions for H(2) production processes and their interaction with the content of total solids in the feed. (C) 2009 Published by Elsevier Ltd on behalf of international Association for Hydrogen Energy.