The effect of different doses (1-50 µ M) of imipramine (IMI) and desipramine (DES) on the rate and force of contraction of isolated rat atria was studied. IMI and DES produced a dose-dependent increase in force of contraction (31- 94% for IMI and 35-118% for DES). Pretreatment of rats with reserpine (5 mg/kg) on the isolated atria with propranolol (1 µ g) inhibited the positive ionotropic effect of both drugs. The two antidepressants IMI and DES showed a dose-dependent decrease in rate of contractions (19-87% and 16-88%, respectively). The positive ionotropic and negative chronotropic effects induced by these drugs was significantly prevented by a selective A₁ antagonist (DPCPX, 3 µ M). The effects of IMI (5 µ M) and DES (5 µ M) the rate and contractile force was inhibited by atropine (10 nM). The selective A₂ antagonist (DMPX, 1.5 µ M) prevented the ionotropic effect produced by IMI and DES. We conclude that in rat atria, the positive ionotropic action of IMI and DES is due to their action on adrenergic, muscarinic, adenosine A₁ and A₂ receptors, and Ca²⁺ influx or release from intracellular storages of the rat myocytes. The negative chronotropic action of these two drugs is probably due to the involvement of adenosine A₁ receptors and cholinergic mechanisms.