In order to select the optimal vasodilator for the treatment of patients with congestive heart failure (CHF), the acute effects of three vasodilators (isosorbide dinitrate (ISDN) 5 mg, nifedipine 10 mg, and prazosin 1 mg) on peripheral capacitance and resistance vessels (CV and RV) were evaluated by a newly devised radionuclear technique (Study 1). Thirty-six patients with chronic CHF were divided into Group A (ejection fraction (EF) greater than or equal to 35%, n = 20, mean EF: 47.2 +/- 6.5%) and B (EF less than 35%, n = 16, mean EF: 24.8 +/- 7.1%). ISDN produced the strongest CV dilatation (25% in both groups). Nifedipine reduced RV tone in Groups A and B (14% and 27%, respectively), and CV tone in Group A (6%). Prazosin had the most prominent effects on both vessels in Group B. From these results, it appeared: (a) ISDN is indicated for the cases with increased CV tone, (b) nifedipine is suitable for those with increased RV tone, (c) in cases of increased tone in both vessels, nifedipine (when EF greater than or equal to 35%) or prazosin (when EF less than 35%) is optimal. To evaluate the validity of this assignment, 49 subjects with CHF were divided into Group 1 (n = 16, increased CV tone), Group 2 (n = 17, increased RV tone), and Group 3 (n = 16, increased CV and RV tone) in Study 2. In Group 1, the changes of all indexes were not significantly different between the subjects treated with optimal drug based on the assignment (subgroup P) and those with a non-optimal drug (subgroup N) after 2 wk of therapy. In Group 2, however, improvements of RV tone, EF, and exercise duration in subgroup P were greater than those in subgroup N (31 versus 10%, 21 versus 0%, 41 versus 14%, respectively). In Group 3, the results were the same as in Group 2 (34 versus 19%, 24 versus 8%, 26 versus 9%). These findings suggested that the selection of the optimal vasodilator based on peripheral hemodynamic evaluation with a newly devised radionuclear technique permits more effective treatment of chronic CHF.