Beta-adrenergic stimulation modulates ventricular currents and sinus cycle length (CL). We tested how changes in CL affect the current induced by isoproterenol (iso) during the action potential (AP) of guinea-pig ventricular myocytes. Methods: Action-potential-clamp was applied at CLs of 250 and 1000 ms to measure 1) the net current induced by 0.1 µM iso (Iiso); 2) the ICa and IKs components of Iiso (IisoCa and IisoK), identified as the iso-induced current sensitive to nifedipine and HMR1556 respectively; 3) Iiso persisting after inhibition of both ICa and IKs (IisoR). IKs pause-dependency and its modulation was evaluated in voltage-clamp experiments. Rate-dependency of APD90 and its modulation by iso were tested in current clamp experiments. Results: at CL = 250 ms Iiso was inward during initial repolarization and reversed at 59% of APD90. At CL = 1000 ms Iiso became mostly inward in all cells. Switching to shorter CL did not change IisoCa and IisoK amplitudes, but moved their peak amplitudes to earlier repolarization; IisoR was CL-independent. Acceleration of IisoK at shorter CL was based on faster pause-dependency of IKs activation rate. The "restitution" of activation rates was modulated by iso. The APD90/CL relation was rotated counterclockwise by iso and crossed the control one at CL=150 ms (400 beats/min). Conclusions: 1) Iso induced markedly different current profiles according to pacing rate, involving CL-dependent ICa and IKs modulation; 2) Iso effect on APD90 was CL-dependent, and negligible during tachycardia; 3) during sympathetic activation, repolarization stability may involve matched modulation of sinus rate and repolarizing currents.