Biohydrogen production from the anaerobic digestion of specified risk materials (SRM) co-digested with cattle manure was assessed in a 3 x S factorial design. Total organic loading rates (OLR) of 10, 20, and 40 g L(-1) volatile solids (VS) were tested using manure:SRM (wt/wt) mixtures of 100:0 (control), 90:10, 80:20, 60:40, and 50:50 using five 2 L continuously stirred biodigesters operating at 55 degrees C. Gas samples were taken daily to determine hydrogen production, and slurry samples were analyzed daily for volatile fatty acid (VFA) concentration, total ammonia nitrogen (TAN), and VS degradation. Hydrogen production (mL g(-1) VS fed) varied quadratically according to OLR (P < 0.01), with maximum production at OLR20, while production decreased linearly (P < 0.0001) as SRM concentration increased. Reduced hydrogen production associated with SRM inclusion at > 10% VS may be attributed to a rapid increase in TAN (r = -0.55) or other inhibitors such as long chain fatty acids. Reduced hydrogen production (P < 0.01) at OLR40 versus OLR20 may be related to increased rate of VFA accumulation and final VFA concentration (P < 0.001), as well as inhibition due to hydrogen accumulation (P < 0.001). Biohydrogen production from SRM co-digested with cattle manure may not be feasible on an industrial scale due to reduced hydrogen production with increasing levels of SRM. Crown Copyright (C) 2009 Published by Elsevier Ltd on behalf of Professor T. Nejat Veziroglu. All rights reserved.