Murine cytomegalovirus (MCMV) induces adrenalitis in BALB/c mice but does not compromise adrenal function, assessed by levels of circulating adrenocorticotropic hormone (ACTH) and by the response to challenge with synthetic ACTH. Levels of corticosterone increased 2 days after infection in mice of this strain, consistent with previously established interactions between mediators of acute inflammation and activation of the hypothalmus–pituitary–adrenal axis. Moreover, an adrenocortical response was critical to survival of BALB/c (but not C57BL/6) mice 3 days after infection, as pharmacologically or surgically adrenalectomized BALB/c mice died when given doses of virus up to fivefold lower than they could normally tolerate. However, death could not be prevented by the administration of soluble cytokine receptors to inhibit the action of interleukin 1 (IL‐1) or tumour necrosis factor alpha (TNFα). The corticosteroid response did not mediate MCMV‐induced thymic atrophy. As the above traits were all less evident in C57BL/6 mice, a common genetic basis is discussed.