Exposure to an enriched environment promotes neurochemical, structural and neurophysiological changes in the brain and is associated with enhanced synaptic plasticity and improved hippocampal-dependent learning. Using a global proteomics-based approach we have now been able to reveal the altered expression of a diverse range of hippocampal proteins following exposure to an enriched environment. Male Hooded Lister rats (8 weeks) were subjected to a 6-week regimen in which they were housed in either non-enriched (open field) or enriched conditions (toys, wheels etc.). Whole protein extracts from stratum pyramidale and stratum radiatum of area CA1 were then isolated and subjected to differential gel electrophoresis [McNair K, Davies CH, Cobb SR (2006) Plasticity-related regulation of the hippocampal proteome. Eur J Neurosci 23(2):575-580]. Of the 2469 resolvable protein spots detected in this study, 42 spots (1.7% of the detectable proteome) derived from predominantly somatic fractions and 32 proteins spots from dendritic fractions (1.3% of detectable proteome) were significantly altered in abundance following exposure to an enriched environment (somatic: 14 increased/28 decreased abundance, range -1.5 to +1.4-fold change; dendritic: 16 increased, 16 decreased abundance, range -1.6 to +3.0-fold change). Following in-gel tryptic digestion and Maldi-Tof/Q-star mass spectrometry, database searching revealed the identity of 50 protein spots displaying environmental enrichment-related modulation of expression. Identified proteins belonged to a variety of functional classes with gene ontology analysis revealing the majority (>70%) of regulated proteins to be part of the energy metabolism, cytoplasmic organization/biogenesis and signal transduction processes.