Background/Aims: Accumulating evidence indicates that capsaicin-sensitive afferent neurons play a pivotal role in acute gastroprotection. by liberating vasodilator substances. The mechanism of gastric protection by honey and sucralfate has been shown to be mediated through the vasodilator nitric oxide and cytoprotective sulphydryl-sensitive pathways in the stomach. The aim of the present study was to investigate the role of capsaicin-sensitive afferent neurons in the protective mechanism of honey and sucralfate against ethanol-induced gastric lesions. Methodology: Ablation of capsaicin-sensitive afferent neurons was carried out by treating rats with neurotoxic doses of capsaicin (50+50 mg/kg subcutaneously over 2 consecutive days). The control groups received equal volumes of the vehicle (10% ethanol Jr 10% Tween 80 + 80% normal saline). The non-protein sulphydryl level was determined spectrophotometrically. Results: Afferent sensory nerve ablation significantly aggravated ethanol-induced gastric lesions and caused a greater depletion of non-protein. sulphydryl levels. Pretreatment with honey (0.078-0.625g/kg, orally) or sucralfate (0.062- 0.250 g/kg, orally) 30 min. before adminitration of the ethanol prevented ethanol-induced gastric lesions and the depletion of non-protein, sulphydryls in. vehicle-treated rats. However, honey failed to afford protection or reverse non-protein sulphydryl depletion, while sucralfate was effective in the capsaicin-treated animals. The protective effect of sucralfate was Lost in both groups following pretreatment with indomethacin (10 mg/kg, subcutaneously), while honey-induced protection was unaffected. Conclusions: These results suggest that the gastric protection by honey is solely dependent on the presence of intact afferent sensory neurons, whereas sucralfate-induced gastroprotection is mediated through theafferent sensory neuron and prostaglandin systems. It seems that the non-protein sulphydryl level is affected by the ablation, of sensory neurons and plays an. important regulatory role in. gastric protection.