Pacemaker generator replacement in dependent patients may be managed with a bridging temporary pacing lead or by replacing the generator very expediently. The 2 options involve a small risk, and temporary pacing introduces additional cost. This study was conducted to explore the utility of a graduated rate-decrease protocol with isoproterenol support in unmasking an intrinsic rhythm that would obviate the 2 strategies. The protocol was used in 100 consecutive pacemaker-dependent patients (mean age 74.4 +/- 13.7 years, 56% men) who underwent permanent pacemaker replacement. Device lower rates were decremented in 1-minute intervals to 60, 50, 40, and 30 beats/min. If no intrinsic rhythm of > or =30 beats/min was observed after 1 minute, isoproterenol was infused at 1 microg/min for 2 minutes, followed by 2 microg/min for 2 minutes. Of the 100 patients, 59 demonstrated intrinsic rhythm during pacing step-down alone. Of the remaining 41 patients, 28 (68.3%) demonstrated intrinsic rhythm during isoproterenol infusion. The escape rhythm was junctional in 29%, idioventricular in 23%, conducted atrial fibrillation in 16%, and sinus in 15%. Only 13 of 100 patients (13%) failed to demonstrate adequate intrinsic rhythm after the protocol. In conclusion, this suggests that a standardized protocol to elicit an underlying rhythm in patients previously assessed as pacemaker dependent effectively minimizes the need for temporary pacing during device replacement.