Gastric and intestinal injury induced by non-steroidal anti-inflammatory drugs (NSAIDs) is a common and expensive adverse effect of this class of drugs. While it is likely that inhibition of prostaglandin synthesis by these agents is an important component of their ulcerogenic properties, the pathogenesis of NSAID gastropathy remains unclear. Likewise, the underlying mechanism for prostaglandin 'cytoprotection' is not fully understood, although it is clear from recent clinical trials that prostaglandin analogues are an effective treatment to prevent NSAID gastropathy. In this paper the contribution of neutrophils to the mucosal damage induced by NSAIDs is discussed, as is the possibility that prostaglandins protect the gastrointestinal mucosa from NSAID-induced ulceration at least in part through inhibitory effects on neutrophil function.