The capsaicinoid spice principles capsaicin and dihydrocapsaicin were shown to be thermogenic in the isolated rat hindlimb perfused with constant flow. Both principles elicited similar maximal increases in oxygen consumption (VO2) and perfusion pressure. For capsaicin, the mean maximal increase in VO2 was 1.39 +/- 0.28 mumol/g h or 23 per cent with a perfusion pressure increase of 15.8 +/- 2.8 mmHg, or 54.5 per cent. Dihydrocapsaicin increased VO2 by 1.13 +/- 0.24 or 20 per cent and a perfusion pressure rise of 14.2 +/- 5.0 mmHg or 49 per cent. Above 0.8 microM of either capsaicinoid there was inhibition of oxygen consumption after transient stimulation. Concurrent infusion of the adrenergic antagonists prazosin (alpha 1) and propranolol (beta) had little or no effect on the actions of either capsaicin or dihydrocapsaicin, nor did division of the somatic nerves to the hindlimb. These results indicate a local site of action of these principles in the hindlimb not mediated by a secondary release of catecholamines. Increases in both VO2 and pressure were significantly blocked by the vasodilator nitroprusside. This is in agreement with our previous findings that nitroprusside can block the effects of angiotensin, vasopressin and flow-induced increases in VO2 and perfusion pressure in the perfused hindlimb. The present findings suggest that capsaicin and dihydrocapsaicin can be thermogenic in the rat and that the mechanism of action directly involves vasoconstriction in some manner. We have previously suggested that there might be significant direct smooth muscle vascular consumption of oxygen during sustained vasoconstriction. The findings with capsaicin and dihydrocapsaicin are consistent with this hypothesis.