Physiological insulin stimulation (induced by re-feeding) in late (19 to 20 days) pregnancy in the rat led to only partial reversal of starvation-induced increases in circulating fatty acid concentrations. The impaired suppression of adipose tissue lipolysis was associated with a clear attenuation of the activation of PDHa activity in oxidative skeletal muscles (diaphragm, soleus and adductor longus) in response to physiological insulin stimulation. In contrast, effects of late pregnancy to suppress glucose utilization were only modest in oxidative skeletal muscles, where a predominate fate of glucose under physiological insulin stimulation is glycogen formation. The ability of the pregnant rat to sustain glycogen repletion during physiological insulin stimulation was retained. Glucose utilization by the heart, which in virgin rats is particularly sensitive to increases in lipid-fuel supply and oxidation, bore a significant inverse relationship with the plasma fatty acid concentrations in late-pregnant rats. We conclude that an elevation in circulating fatty acid concentrations in late pregnancy provokes changes in glucose utilization by cardiac and skeletal muscle which are consistent with the operation of the glucose-fatty acid cycle. Importantly, these effects pertain under physiological hyperinsulinaemia. The relative insensitivity of glucose utilization by oxidative skeletal muscle to late pregnancy under conditions of physiological insulin stimulation presumably reflects the predominant use of glucose as a substrate for glycogen synthesis rather than as an energy substrate.