It is questioned whether alterations of the sympathetic nervous system can explain the specific increment of the adipocyte alpha 2-adrenoceptor observed during white adipose tissue (WAT) enlargement and fat cell size increment. The impact of a 6-hydroxydopamine-induced sympathectomy, validated by determination of the WAT norepinephrine content, was tested on isolated white fat cell alpha 2-adrenoceptor function and binding [( 3H]RX 821002 and [3H]UK 14304 binding). Chemical sympathectomy of standard adult hamsters, neither alters the alpha 2-adrenergic-dependent antilipolysis nor the adipocyte alpha 2-adrenergic binding. A slight hypersensitivity of the beta 1-adrenergic lipolytic response was observed, without modification in beta-adrenergic binding [( 125I]cyanopindolol binding). Compared with controls, caloric restriction (10 days) of adult hamsters induced a large decrease in adipocyte alpha 2-adrenoceptor (P less than 0.001) with a parallel decrement in the mean fat cell size (P less than 0.001) and alpha 2-adrenergic responsiveness while there was no significant variation of the WAT norepinephrine content (on a per pad basis). 6-Hydroxydopamine treatment of the restricted animals (from day 6 to day 9) induced a higher preservation of adipocyte alpha 2-adrenoceptor density (P less than 0.001), no change in alpha 2-adrenergic responsiveness, and higher preservation of mean fat cell size (P less than 0.05) than in the restricted only animals. No significant modification in the beta-adrenergic binding was observed whatever the conditions. It was concluded that the specific increment in the adipocyte alpha 2-adrenoceptor during fat mass enlargement was not directly dependent on sympathetic nervous system alterations. Nevertheless, the sympathetic-dependent mobilization of the fat stores, after induction of caloric restriction, can indirectly modulate the alpha 2-adrenoceptor density in the adipocyte by promoting changes in white fat cell size.