Hemodialysis (HD) has been associated with an increase in the amplitude of QRS complexes. Experience in a single patient with multiple measurements has shown that HD leads also to augmentation of P-wave amplitude. The objective of this investigation was to evaluate electrocardiogram (ECG) changes with HD in a cohort of patients undergoing this procedure with particular emphasis on the P-wave and QRS complex changes. The sum of amplitudes of P waves (OP) and QRS complexes (OQRS) in millimeters in the 12 leads of the ECG, along with a host of other ECG parameters, body weight, blood pressure, heart rate, electrolytes, and hemoglobin/hematocrit were measured before and immediately after HD in 47 patients. Hemodialysis resulted in a loss of a mean of 3 kg of weight and an increase in the SigmaP, SigmaQRS, mean QRS duration, maximum P-wave duration, and P-wave duration measured in lead II, whereas the changes in mean P-wave and corrected QT interval durations were not statistically significant. Percentage change (Delta%) in SigmaP and SigmaQRS correlated poorly with Delta% in electrolytes, hematocrit, blood pressure, heart rate, and weight. Values for SigmaP and SigmaQRS vs weight were r = 0.105, P = .48 and r = 0.09, P = .51, respectively. The Delta% in SigmaP correlated well with Delta% in SigmaQRS (r = 0.42, P = .003). Alterations in P-wave amplitudes and duration commensurate with the ones affecting the corresponding QRS complexes occur in patients undergoing HD and indicate that evaluation of measurements in serial ECGs should take this into account. The mechanisms of these phenomena continue to be elusive, and whether they represent cardiac and/or extracardiac influences has not as yet been unraveled.