Fasting and thyroid hormone have been reported to modulate the beta-adrenergic pathway of lipolysis in rat, but their effects on the alpha 2-adrenergic response are not well known. The purpose of the present study was to investigate this point. Male Wistar rats, 3 weeks old, were thyroidectomized surgically, kept for 1 month at 25 degrees C and then fasted or not fasted for 3 days with or without daily intraperitoneal injection of 3,5,3'-tri-iodo-L-thyronine (T3; 4.6 nmol/100 g body weight). Age-matched, sham-operated, fed and fasted euthyroid rats were used as controls. The experiments were carried out using isolated epididymal adipocytes. The alpha 2-adrenergic agonist UK 14304 (UK) inhibited the stimulated lipolysis more in fed than in fasted euthyroid rats whereas it had no effect in hypothyroid or T3-treated hypothyroid rats. The alpha 2-adrenergic antagonist idazoxan reversed the antilipolytic effect of UK more in fasted than in fed euthyroid rats. The alpha 2-adrenergic antagonist RX 821002 (RX) did so, but at lower concentrations than those of idazoxan. Idazoxan slightly increased the glycerol release in hypothyroid and especially T3-treated hypothyroid rats. RX had practically no effect on the production of glycerol in these animals. The findings suggest that (a) fasting and probably hypothyroidism decrease the alpha 2-adrenergic response in adipocytes from rats, (b) T3 treatment of hypothyroid rats has no effect on the alpha 2 response, and (c) thyroid hormone does not directly modulate the alpha 2-adrenergic response in rat adipocytes.