The present study was designed to assess effectiveness and safety and the proarrhythmic effects of two methylxanthine derivatives, doxofylline and aminophylline, in the management of chronic obstructive pulmonary disease associated with cardiac rhythm disturbances. Fourteen patients of both sexes (9 male, 5 female) with a mean age of 54 (range 43 to 66 years) with concomitant chronic obstructive pulmonary disease and high incidence of ventricular (VPB) and/or supraventricular (SVPB) premature beats were selected. The study was performed in a double-blind randomized cross-over trial. Following a proper wash-out period, in each phase patients were administered intravenously 400 mg b.i.d. of doxofylline or 480 mg of aminophylline b.i.d. (rate of infusion: 60 min) according to the cross-over design. A 24-hour Holter monitoring was carried out before the onset of the treatments and at the end of each venous infusion of methylxanthines. Spirometry for measurement of forced expiratory volume in one second and clinical parameters were also evaluated. Parametric variables were evaluated by analysis of variance. Kruskal-Wallis test was used to estimate non parametric variables. A p value less than 0.05 was considered statistically significant. We observed a significant reduction in the occurrence of VPB/24 h (p less than 0.05 vs basal value) and in the total number of beats (p less than 0.01 vs basal value and p less than 0.05 vs aminophylline) after doxofylline administration, whereas no changes from baseline in the incidence of premature beats and in the mean 24-hour heart rate were reported after aminophylline.(ABSTRACT TRUNCATED AT 250 WORDS)