Sixteen patients with multifocal atrial tachycardia (MAT) who were taking theophylline were identified over 6 months. After theophylline was discontinued the atrial rate fell and MAT resolved in all sixteen patients. Five patients were challenged with intravenous aminophylline to investigate the role of theophylline in the genesis of MAT. MAT with a rapid ventricular response occurred in all five even though metabolic and respiratory variables did not change. MAT returned on challenge in three patients in whom serum theophylline levels were within the generally accepted therapeutic range (10-20 mg/l). In individual patients, theophylline had a dose-related effect on the atrial rate and the amount of ectopic atrial activity. Thus, theophylline may commonly precipitate MAT and treatment with the drug should be carefully considered in patients with respiratory insufficiency and MAT.