We recently observed a strong increase of 5’-nucleotidase in renal fibroblasts of rats that were anemic due to an immunity against erythropoietin. In order to test if the change of 5’-nucleotidase was related with anemia, we studied the distribution of the enzyme in irradiated rats treated with phenylhydrazine. The hematocrit of these rats decrased to 15% within 4 days and erythropoietin levels were more than 200 times over controls. After 7 days a histochemical study showed that the enzymatic activity and the immunoreactivity for 5’-nucleotidase was markedly enhanced in the fibroblasts of the cortical labyrinth. There was no modification of 5’-nucleotidase in other cell types of the kidney. The 5’-nucleotidase activity of renal fibroblasts in cell culture increased by 72% upon addition of 160 µM 5’-AMP to the culture medium for 8 days. We propose that anemia provokes an energy deficit in some structure in the cortical labyrinth. This might increase the concentration of 5’-AMP which would induce 5’-nucleotidase. An interesting consequence of these events would be an increased production of adenosine in the direct vicinity of some of its putative targets, the glomerular arterioles and the erythropoietin