In this study glutathione (GSH), a natural tripeptide which plays an important role in detoxification reactions, protecting cells against damage from xenobiotics, has been labelled with 99Tc(m) for the demonstration of head and neck cancer. Twenty-eight patients (10 females and 18 males) with various malignancies of the head and neck were given 740 MBq of 99Tc(m)-GSH intravenously and single-photon emission computed tomography (SPECT) images were obtained at 3 h. Semiquantification was performed by drawing regions of interest on three consecutive transaxial slices and tumour to background ratios were calculated. In addition, GSH and glutathione S-transferase (GST) levels were measured in the tumour samples and in normal tissue which were obtained during surgery. Scintigraphic images showed that there was increased uptake in the tumour compared to the normal contralateral side (tumour/normal tissue (mean +/- SD) = 1.94 +/- 0.76). The tissue analyses revealed increased levels of GST in tumour tissues, but both GST and GSH levels in tumour were not statistically different from those in the normal tissue. We conclude that scintigraphic visualization of head and neck tumours can be attributed to increased demand for GSH in cancer. Protein binding might account for the prolonged retention of 99Tc(m)-GSH in the malignant tissue. Like other peptides, it is accumulated and excreted by the kidneys, which allows clear visualization of the abdomen without interference from gastrointestinal system activity.