The aim of this study was to demonstrate significant factors behind elevated resting energy expenditure in weight-losing cancer patients. Therefore, weight-losing cancer patients (n = 60), with normal liver and kidney function tests, were randomized to receive one of four drug treatments for 5 days: (a) Propranolol 80 mg x 2 (beta-adrenoceptor blockade); (b) Indomethacin 50 mg x 2 (prostaglandin synthesis inhibition); (c) Morphine 5 mg x 3 (pain relief) or (d) Placebo x 2. A reference group of healthy well-nourished individuals were examined outside the formal randomization protocol and they received Propranolol 80 mg x 2. The cancer patients were randomized by a computer based algorithm stratifying for measured resting energy expenditure (REE), body composition, biochemical tests, previous therapy, tumour type and tumour stage. Resting energy expenditure was measured by indirect calorimetry in the morning after an overnight fast before and after drug treatment. beta-blockade reduced REE significantly in cancer patients from 1416 +/- 95 kcal day-1 to 1160 +/- 63 kcal day-1 (P < 0.02) and from 1472 +/- 69 vs, 1398 +/- 63 kcal day-1 (P < 0.01) in the well-nourished reference individuals. The reduction found in cancer patients (10%) was significantly larger than that in the group of reference patients (5%), (P < 0.01). Indomethacin, morphine or placebo did not induce any significant alteration in energy expenditure in our cancer patients. Propranolol treatment was associated with a significant reduction in plasma concentrations of free fatty acids (FFA), but not in plasma glycerol.(ABSTRACT TRUNCATED AT 250 WORDS)