In the current study our objective was to develop a murine model of human hyper‐IgD syndrome (HIDS) and severe mevalonic aciduria (MA), autoinflammatory disorders associated with mevalonate kinase deficiency (MKD). Deletion of one Mvk allele (Mvk^+/−) yielded viable mice with significantly reduced liver Mvk enzyme activity; multiple matings failed to produce Mvk^−/− mice. Cholesterol levels in tissues and blood, and isoprene end‐products (ubiquinone, dolichol) in tissues were normal in Mvk^+/− mice; conversely, mevalonate concentrations were increased in spleen, heart, and kidney yet normal in brain and liver. While the trend was for higher IgA levels in Mvk^+/− sera, IgD levels were significantly increased (9–12‐fold) in comparison to Mvk^+/+ littermates, in both young (<15 weeks) and older (>15 weeks) mice. Mvk^+/− animals manifested increased serum TNF‐α as compared to wild‐type littermates, but due to wide variation in levels between individual Mvk^+/− mice the difference in means was not statistically significant. Mvk^+/− mice represent the first animal model of HIDS, and should prove useful for examining pathophysiology associated with this disorder.