Erythropoietin (EPO) is a glycoprotein that stimulates red blood cell production and the kidney is the major source of EPO production. We examined the effects on serum EPO concentration of a low (8.5%) casein diet (8.5C), nephritis induction, and supplementation of the limiting amino acids, 0.3% L-methionine and 0.36% L-threonine, to the low casein diet (8.5CMT), using a 20% casein diet (20C) as the control. Nephritis was induced in rats by an intravenous injection of anti-rat kidney glomerular basement membrane rabbit antiserum. Serum EPO concentration decreased when normal rats were fed the 8.5C, and this decrease was quickly restored when refed the 20C or 8.5CMT. Serum EPO concentration was significantly lower in 20C-fed nephritic rats than in 20C-fed normal rats. In the nephritic state as well as the normal state, serum EPO concentration was significantly decreased in the 8.5C-fed animals compared with the 20C-fed ones. This fall in serum EPO was restored to the concentration of 20C-fed rats by 8.5CMT feeding. The 8.5CMT also reduced proteinuria and hypercholesterolemia in nephritis without the severe growth retardation. These results suggest that the dietary manipulation of 8.5CMT has a diversity of beneficial effects on nephritis.