To identify the metabolic effects of 5-fluorouracil and hydrazine sulfate therapy, 22 patients with colon cancer were admitted prospectively to a Clinical Research Center for serial measurement of counter-regulatory hormones, fasting hepatic glucose production (HGP), intravenous glucose tolerance test, plasma leucine appearance (LA) and leucine oxidation. Combined therapy was associated with a significant reduction in fasting glucose level (98 +/- 2 mg/dL to 94 +/- 2, P < 0.025) without a significant fall in fasting HGP (2.09 +/- 0.11 mg/kg/min versus 2.03 +/- 0.13; P > 0.05). The decreased fasting glucose value was associated with a mild but not statistically improved glucose disposal rate in response to the intravenous glucose tolerance test (1.34 +/- 0.07 %/min vs 1.47 +/- 0.11, P = 0.15). Plasma leucine appearance was significantly reduced after 2 months of therapy (63.3 +/- 3.0 mumol/kg/hr vs 57.1 +/- 3.9 mumol/kg/hr; P < 0.025), but leucine oxidation (11.5 +/- 1.1 mumol/kg/hr vs 11.2 +/- 1.1 mumol/kg/hr) was not altered. Despite the fact that plasma triiodothyronine concentrations significantly increased with therapy, it was not associated with plasma LA. Half of the patients with cancer died 14 +/- 4 months after the study, and the other half were alive 58 +/- 2 months later. Survival time can be estimated with 59% accuracy using plasma LA, HGP, carcino-embryonic antigen, and insulin concentration. Multiple regression analysis identified that plasma LA was related directly to length of survival time, and baseline HGP, carcino-embryonic antigen, and insulin concentration were related inversely to length of survival.(ABSTRACT TRUNCATED AT 250 WORDS)