Critical illness is associated with catabolism caused by the alteration of several hormonal systems. Low levels of insulin-like growth factor I (IGF-I) in critical illness are observed despite increased or normal levels of growth hormone (GH). The mechanisms for this apparent GH resistance have not been elucidated. Since proinflammatory cytokines mediate many of the acute responses in critical illness, we evaluated the effects of IL-1 beta and TNF-alpha on growth hormone receptor-(GHR-)mRNA in cultured rat hepatocytes. Diminished GHR-mRNA concentrations in response to cytokine stimulation indicate that low IGF-I levels in the beginning of severe illness, may at least be partially a cause of GHR synthesis suppression by proinflammatory cytokines.