The effects of a low-casein diet fortified with methionine and threonine on renal cortical and glomerular transforming growth factor (TGF)-beta activity were studied in rats with nephritis induced by anti-rat kidney glomerular basement membrane antiserum. Both normal and nephritic rats were fed experimental diets for 10 days. An injection of nephrotoxic serum increased urinary protein excretion and renal TGF-beta activity. A methionine-threonine-supplemented 8.5% casein diet, compared with a basal 20% casein diet, decreased these two measurements without aggravating growth retardation in nephritic rats. These results suggest that aggravation and alleviation of symptoms incident to anti-GBM nephritis are relevant to elevation and reduction of TGF-beta activity, respectively. The results also suggest that amino acid-balanced low-protein diets would have beneficial effects on glomerulonephritis without causing severe protein malnutrition.