The purpose of this study was to find out whether the glutathione (GSH), in red blood cells could predict the response to neoadjuvant chemotherapy cisplatin/5-fluorouracil (CDDP/5-FU) in patients with head and neck squamous cell carcinoma (HNSCC). Three courses of induction chemotherapy with CDDP/5-FU were administered and followed by surgery and radiotherapy or radiotherapy alone, in 51 patients with HNSCC. GSH was measured by spectrophotometry in red blood cell before any treatment (Sample 1: S1), after each course of chemotherapy (S2, S3, S4). Our results showed that GSH was the same at diagnosis in patients with complete or partial response (OR) compared to those with stable or progressive disease (NR). With regard to evolution of the GSH during the 3 courses of CT a significant difference was found between courses (S2: 5.06 +/- 0.35 vs S4 = 3.61 +/- 0.4 mumol/g haemoglobin, p < 0.05). When we separated our patients into OR and NR, a significant difference was found over the 3 courses of chemotherapy for GSH content. Non responder patients showed decreased GSH content at the end of the treatment, (S2: 5 +/- 0.5 vs S4: 2.2 +/- 0.4 mumol/g haemoglobin, p < 0.05) while OR were stable. In conclusion, red blood cell GSH seems to have no early predictive value for chemoresponse to neoadjuvant chemotherapy CDDP/5-FU in HNSCC.