We studied alpha-aminoisobutyric acid (AIB) transport by skeletal muscle and the effect of insulin and Na+ on the transport process during endotoxic shock. Rats (140-160 g) were injected with Salmonella enteritidis endotoxin (20 mg/kg iv) or saline and killed 5 h later. At that time an elevation of blood lactate and hypoglycemia marked the onset of shock in rats given endotoxin. AIB uptake was measured in isolated soleus muscles in vitro. Total cellular AIB uptake in the endotoxic muscles was 25, 28, and 47% lower than control muscles at 1-, 2-, or 3-h incubations, respectively. Insulin stimulated AIB uptake to a lesser extent in endotoxic muscles (from a basal value of 11.62 +/- 0.29 nmol X g dry wt-1 X 3 h-1 to 15.88 +/- 0.64, 19.10 +/- 1.06, and 18.78 +/- 0.52 at 1, 10, and 100 mU/ml insulin, respectively) than in controls (from 17.07 +/- 0.51 to 27.13 +/- 1.16, 27.25 +/- 0.93, and 29.01 +/- 1.09). Na+-dependent AIB uptake, calculated as the difference between AIB uptake in the presence and absence of Na+, was decreased in the endotoxic muscles to 36% of the control value. Na+-independent AIB uptake (measured in Na+-free media) was the same in control and endotoxic muscles. These results suggest that the decrease in both basal and insulin-stimulated AIB transport was due to the decrease in Na+-dependent AIB transport by skeletal muscle during endotoxic shock.