The effects of protein deprivation on erythropoietin (Ep) production were studied. The posthypoxia plasma Ep levels of rats fed a protein- free diet for only 1 day prior to being exposed to 0.5 atmosphere for 7 hr were significantly lower than those of comparably hypoxic rats maintained on a normal diet. The postthypoxia plasma Ep levels were even lower in rats kept on protein-depleted diets for longer periods of time. Rats fed diets with 0.5%, 5% or 12% protein content for 6 days had lower posthypoxia plasma Ep levels than those fed a normal diet (20% protein content). When a single protein meal was force-fed to protein-deprived rats 0–4 hr after initiating the exposure to hypoxia, the posthypoxia plasma Ep levels were significantly higher than in protein-deprived rats that were fed water or dextrose. The posthypoxia plasma Ep titers of protein-deprived rats fed protein 4–8 hr prior to exposure to hypoxia did not differ significantly from those of protein- deprived rats. Although the posthypoxia plasma Ep levels of protein- deprived rats fed a hemolysate containing 0.8 g of hemoglobin 4 hr after beginning hypoxia were greater than those of protein-deprived rats fed only water, the rate of oxygen consumption in these two groups did not differ. We conclude that, in addition to its response to the availability of oxygen, Ep production is infl,enced by the availability of amino acids.