AbstractClinical failures of central nervous system fluid shunts remain a vexing problem. Attributed largely to infectious and technical etiologies, it has been hypothesized recently that inflammatory mechanisms may play a role in this clinical phenomenon. In order to obtain morphologic evidence for this hypothesis, a study of failed shunts was performed. Twenty‐five of 57 sequentially removed CNS fluid shunt assemblies or components over the course of 18 months contained sufficient intraluminal tissue to allow a histomorphologic assessment. Tissue was removed from either the intraventricular or intraperitoneal portion and examined with routine light microscopical and histochemical techniques to assess the degree of cellularity, composition of the cells, presence of debris, and organisms. Morphologic findings were correlated with the clinical courses and microbiological cultures. Data were analyzed nonparametrically using the χ2test. There was a substantially significant association between repeated failures and non‐infectious obstructions. Eight demonstrated evidence of active inflammatory processes; and although not statistically significant, the presence in 3 cases of giant cells, macrophages, lymphocytes, and eosinophils all suggestive of a hypersensitivity reaction correlated with the occurrence of culture negative clinical failures. These morphologic findings will stimulate further experimental and clinical research into possible inflammatory mediators of shunt fai