High plasma levels of estradiol are known to reduce the GDP binding of brown adipose tissue. Since GDP binding depends on the level of sympathetic discharge to brown adipose tissue, we measured the responsiveness to noradrenaline of brown adipocytes isolated from female rats with high plasma levels of estradiol. Noradrenaline responsiveness was assessed by measuring the respiration rate of isolated brown adipocytes in the presence of different concentrations of noradrenaline. Both control and treated adipocytes showed the same basal respiratory rate (27 +/- 6 and 24 +/- 4 nmol O2.min-1.10(-6) cells, respectively). The presence of noradrenaline (0.1, 1, and 10 microM) in the medium increased the respiration rate of both kinds of adipocytes in a dose-dependent manner. However, the response was markedly reduced in adipocytes isolated from estradiol-treated rats. These results suggest that estradiol impairs the responsiveness of brown adipose tissue to the sympathetic nervous system. Three possible mechanisms are suggested as accounting for the observed decreased responsiveness to noradrenaline, i.e., a direct action of estradiol in brown adipocytes, a modulatory role of estradiol in the central control of the sympathetic discharge to brown adipose tissue, and the interference of catecholestrogens with noradrenaline synthesis at the sympathetic terminals.