"Mild irritants" have been shown to protect rat gastric mucosa from damage induced by noxious topical agents, supposedly by induction of mucosal prostaglandin (PG) biosynthesis. The protective effect of NaCl 5%, ethanol 20%, NaOH 0.075 N, HCl 0.35 N, salicylic acid 100 mg/kg and paracetamol 200 mg/kg was investigated in rats treated with an ulcerogenic dose (25 mg/kg) of indomethacin; mucosal PG synthesis was simultaneously determined. Significant protection was achieved only with NaCl 5%, salicylic acid and paracetamol. Salicylic acid and paracetamol significantly decreased acid secretion and enhanced PGE2 or 6-keto PGF1 alpha generation in control rats, while a small but significant change in the indomethacin-inhibited PG synthesis was observed after treatment with NaCl 5% or salicylic acid. We conclude that protection by "mild irritants" against indomethacin-induced mucosal damage may involve increased cytoprotective PG generation, as shown for paracetamol and salicylic acid, or partial blocking of indomethacin binding at the cyclooxygenase receptor site, as shown for NaCl 5% and salicylic acid.