We evaluated the effects of combined therapy with anti-inflammatory and antioxidant drugs on the healing of radiofrequency (RF) lesions (70 degrees C, 60 s) produced in the right atrium and each ventricle of 21 adult dogs. Three groups were studied: acute (n= 7, sacrificed 1 hour after RF); control (n = 7, sacrificed 54 +/- 29 days after RF); and dogs (n = 7, sacrificed 32 +/- 5 days after RF) receiving combined therapy with allopurinol (400 mg p.o. 24 and 2 hours before RF); verapamil (200 microg/kg i.v. 15 min before and after RF); hydrocortisone (10 mg/kg i.v. after RF) and prednisone (20 mg p.o. for 29 days). Atrial (n = 37) and ventricular (n = 70) lesion dimensions were determined and 21 right ventricular apex lesions (1 per dog) were selected for light and electron microscopy analysis. Histological and ultrastructural (US) characteristics in three zones extending from the visible lesion border, A (0-3 mm); B (3-6 mm); and C (6-9 mm), were assessed. In chronic groups, atrial and ventricular lesion dimensions were similar, but delayed scar formation was noted in treated animals. Acutely and at follow-up, significant US abnormalities occurred in zones A and B and chronic lesions exhibited type I collagen proliferation. In Zone A, the extent of US injury and collagen proliferation was significantly less in treated dogs. Further, Zone B was normal in 5/7 (71%) treated dogs and in 0/7 (0%) controls. Zone C was essentially normal in all groups. Combined therapy with steroids, verapamil, and allopurinol is effective in limiting US damage surrounding chronic RF lesions.