The effect of sustained endotoxemia on expression of the acid-labile subunit (ALS) in relation to hepatic markers of altered GH and insulin-sensitivity was examined. Juvenile rats were injected with endotoxin twice-daily for 48h, causing reduced food-intake and attenuated growth. In pair-fed controls, food restriction caused marked suppression of ALS gene expression and circulating levels within 12h, and endotoxemia augmented this effect. This acute effect of endotoxin corresponded temporally with transient induction of SOCS-3, CIS, PEPCK and IGFBP-1 and suppression of GH-receptor. During the subsequent 36h of sustained endotoxin treatment, expression of ALS recovered to, then rose above that of their pair-fed controls. This effect was paralleled by other ternary complex components. The inductive effect of sustained endotoxemia relative to pair-fed controls could not be explained by differences in expression of GHR, SOCS-3 or CIS, but coincided with normalized PEPCK and IGFBP-1 levels, suggesting better hepatic insulin-sensitivity in these animals. These data may indicate that in sustained endotoxemia ALS levels are regulated through modulation of hepatic insulin-sensitivity.