Isosorbide dinitrate ointment (100 mg tid) was directly applied to 30 male patients with stable, documented intermittent claudication on the areas where ischemic pain was experienced. The symptom-free distance walked (DWA) and the maximum distance reached (MDR) basally, after one, three, six, and twelve months were evaluated by means of treadmill stress tests (TSTs) (angle 0 degree-velocity constant/patient). After the basal TST, patients were randomly divided into two groups: placebo group and therapy group (double blind), and a further TST was administered one month later. DWA results were 74 +/- 8 m vs 297 +/- 83 m and MDR results were 163 +/- 22 m vs 506 +/- 86 m in the therapy group (basal vs one month TST: p less than .01) and 94 +/- 24 m vs 96 +/- 15 m and 232 +/- 53 m vs 183 +/- 26 m in the placebo group, respectively (basal vs one month TST: NS). Being confident that a significant placebo effect was absent, the authors opened the trial and treated all patients, repeating further TSTs at three, six, and twelve months. The following results were obtained: DWA was 84 +/- 13 m, 316 +/- 63 m, 374 +/- 55 m, and 452 +/- 61 m; and MDR was 197 +/- 29 m, 431 +/- 59 m, 514 +/- 57 m, and 547 +/- 59 m, respectively, in basal conditions and after three, six, and twelve months of treatment (p less than .01 for all the values for both DWA and MDR vs basal values).(ABSTRACT TRUNCATED AT 250 WORDS)