Cardiac arrhythmias are noted in a significant proportion of chronic renal failure (CRF) patients on hemodialysis (HD), and may contribute to cardiovascular mortality. A number of factors have been implicated in the genesis of these arrhythmias. The role of silent myocardial ischemia (SMI), however, has not been evaluated systematically. We prospectively studied 38 unselected CRF patients on regular HD by continuous Holter monitoring starting 24 hours before HD, lasting through the dialysis session and continued for 20 hours thereafter. The recordings were analyzed for frequency, timing and severity of supraventricular and ventricular arrhythmias and SMI as identified by ST-segment depression. Ventricular arrhythmias during HD were noted in 11 (29%) patients (group I), and were potentially life-threatening (Lown Class III and IVa) in 13%. The remaining 27 patients (group II) had no ventricular arrhythmias during HD. There was no difference in the age, sex ratio, duration of HD, blood pressure, fluctuations in weight, hematocrit, predialysis creatinine, sodium, potassium, calcium or inorganic phosphate levels between patients in the two groups. The number of patients with clinical ischemic heart disease was significantly greater in group I. SMI was noted in 72% and 33% of group I and II patients respectively (p = 0.026). 46% of those with and 25% of those without ST changes during HD developed ventricular arrhythmias during HD. Both SMI and ventricular arrhythmias were noted most frequently during the last hour of dialysis. Hypertension, diabetes mellitus and ischemic heart disease were observed more frequently amongst patients with SMI. Ventricular arrhythmias are detected in a significant proportion of CRF patients on HD. These are probably related to coronary artery disease since silent myocardial ischemia is also noted more frequently during HD in these patients. Further studies incorporating coronary angiography are needed in a larger number of patients to establish a definite causal relationship.