The use of streptomycin in the PrPsc detection procedures represents a new and attractive way to detect more PrPsc, the best marker for the transmissible spongiform encephalopathies (TSEs). Actually, the streptomycin PrPsc aggregating property reported recently was established as beneficial in PrPsc detection using immunohistochemistry in diagnostic as well as in experimental conditions. The present study reports in details how to use advantageously this original streptomycin property in PrPres biochemical extraction and detection. Using TSE diagnostic brain material, specificity and increased sensitivity using streptomycin-treated samples were substantiated. Then an early sequential brain and spleen sampling (from 7 to 49 days post-inoculation) from C57B1/6 mice inoculated intra-cerebrally or intra-peritoneally with C506M3 scrapie strain was analysed using streptomycin versus ultracentrifugation PrPres extraction. Whatever the inoculation route, streptomycin allowed earlier PrPres detection in spleen (7 d.p.i.), then in brain suggesting a stronger affinity of the infectious agent for the lymphoid compartment. (C) 2008 Elsevier Inc. All rights reserved.