Peripheral tissue resistance to insulin-mediated glucose uptake occurs in uremia. A similar resistance also may exist to insulin-mediated amino acid uptake. The present study examined the effect of insulin on the uptake or distribution ratios (DR) of alpha-aminoisobutyric acid (AIBA) attained in the tissues of rats made acutely uremic by bilateral nephrectomy. Both uremic and control rats concentrated equally AIBA in the gastrocnemius muscle in the absence of insulin (DR = 2.82 +/- 0.39 in controls, 2.52 +/- 0.40 in uremics). Compared to control rats, the diaphragm and liver of uremic rats, in the absence of insulin, had higher concentrations of AIBA. Insulin had the expected effect of increasing the uptake in the gastrocnemius, diaphragm, and liver of control rats but had no effect on uptake in the gastrocnemius muscle of uremic rats (DR = 5.82 +/- 0.78 in controls, 3.07 +/- 0.60 in uremics). The effect of insulin on the distribution ratio of AIBA in diaphragm and liver or uremic rats was less than it was in control rats. Uremia is associated with inhibition of insulin-mediated amino acid uptake as well as peripheral resistance to glucose utilization.