A model system that has the potential to enhance our understanding of cardiac hypertrophy is the response of the fish heart to thermal acclimation. Salmonid fishes (like rainbow trout, Oncorhynchus mykiss) are ectothermic and remain active in waters that vary seasonally between 4°C (winter) and 20°C (summer). In response to prolonged cooling there is an increase in relative ventricular mass that is thought to help compensate for the influence of low temperature on contraction and the increased work required to pump cold viscous blood about the body. We exploited this natural physiological hypertrophic system and assessed functional, morphological, and gene/protein expression changes associated with thermal acclimation in trout ventricle. Trout were thermally acclimated to 4, 11 or 18°C for a minimum of 1 month prior to experimentation. Fish were humanely killed in accordance with UK legislation and hearts excised and either used for functional studies or to investigate protein and gene expression. We show a significant upregulation (P<0.05, 2-way ANOVA) of a number of pro-hypertrophic markers after cold acclimation including ventricular myosing heavy chain (VMHC), muscle LIM protein (MLP) and smooth muscle light chain (SMLC2) and regulator of calcineurin (RCAN), a marker of pro-hypertrophic NFAT signalling. These gene expression changes are associated with significant (P<0.05, 2-way ANOVA) cold-induced increases in collagen and decreases in elastin, that correlate well with functional changes in ventricular compliance. We also show cold induced remodelling of conduction pathways with associated changes in gap junction mRNA level changes. These results suggest the trout heart is a good model for mammalian hypertrophy. Because the hypertrophic response in fish is transient (seasonal) we believe this system can provide insight into pathways for hypertrophic recovery in mammals.