1. The metabolic response of lean and obese women to caffeine was studied to see if caffeine could be used to demonstrate the subnormal thermogenesis in obesity previously shown after standard meals or intravenous infusions of noradrenaline.
2. The rise in resting metabolic rate with caffeine was similar in the lean and obese groups and β-adrenoceptor blockade did not reduce the increment in metabolic rate in either group. These responses did not, therefore, correspond with the other subnormal thermogenic responses of the constitutionally obese.
3. In a post-obese group, i.e. previously obese women who were now of normal weight, there was a reduced response of the resting metabolic rate to caffeine.
4. Monitoring plasma substrate concentrations showed that the change in oxygen uptake corresponded to changes in plasma free fatty acids, so that in adults the metabolic effects of caffeine seem to be mediated by increases in adipocyte lipolysis. This effect seems to be mainly independent of the adrenergic system.