Antitachycardia devices need more accurate means to identify arrhythmias. Previous studies have found that sinus rhythm can be distinguished from a variety of tachyarrhythmias by algorithms that are based on time-domain and frequency-domain analysis of intracardiac electrograms. Amplitude distribution analysis (time-domain) and power density spectral analysis (frequency-domain) are two of the techniques that have seemed to hold promise. However, previous studies have not evaluated whether lead maturation or drugs such as lidocaine, propranolol, verapamil, or isoproterenol can interfere with the ability of these algorithms to distinguish among cardiac rhythms. In the present study, five dogs had permanent atrial pacing leads placed. On a series of days, recordings were made from the atrial leads during sinus rhythm and induced sustained atrial fibrillation, both before and after administration of cardioactive drugs. For up to 1 month after implantation, progressive lead maturation did not prevent differentiation of atrial fibrillation from sinus rhythm by either amplitude distribution analysis or power density spectral analysis. However, the difference between the power density spectra of sinus rhythm and atrial fibrillation became progressively less with time. Isoproterenol, lidocaine, verapamil, and propranolol had no consistent effects on amplitude distribution analysis of atrial electrograms during sinus rhythm or atrial fibrillation. However, there were marked effects of drugs on amplitude distribution characteristics in individual dogs. Propranolol and lidocaine produced consistent changes in power density spectra during sinus rhythm and atrial fibrillation, respectively; both drugs reduced the ability of power density spectral analysis to differentiate sinus rhythm from atrial fibrillation.(ABSTRACT TRUNCATED AT 250 WORDS)