BACKGROUND Previous studies have shown that a methionine-lacking diet inhibited tumor growth in rats. The aim of this study was to determine how methionine free total parenteral nutrition (MTPN) can result in the inhibition of tumor growth on tumor protein metabolism in rats. METHODS On day 0, AH109A rat ascites hepatoma cells were implanted subcutaneously into male Donryu rats (n = 68, body weight, 200-225 gm). On day 10, a catheter for total parenteral nutrition (TPN) was placed and either MTPN or standard TPN solution was given for 5 days. On day 15, 1-14C-leucine was infused continuously to measure tumor protein synthesis. Tumor proteolysis was calculated from tumor regional blood flow, using the 85Sr-microsphere injection method. RESULTS 1) Tumor weight was reduced with MTPN. 2) MTPN did not affect tumor protein synthesis, probably because endogenous methionine production was increased with MTPN (87.3 +/- 13.5 mumole methionine/kg/hour vs. 218.6 +/- 29.5, P < 0.01); however, MTPN caused an increase of tumor proteolysis (2.68 +/- 0.53 mumole leucine/g/hour vs. 3.79 +/- 0.73, P < 0.05). CONCLUSIONS The enhanced tumor protein breakdown contributed to the inhibition of tumor growth that was found with the rats given the methionine free diet.