We conducted a double-blind trial with the calcium antagonist, diltiazem (8 mg/kg/d), for 24 to 32 months in 22 boys with Duchenne muscular dystrophy, who were paired by functional activity and age. No adverse clinical or ECG effects of diltiazem were detected. In eight matched pairs, completing 28 months, manual muscle testing scores fell somewhat less in the diltiazem group (from 5.5 to 4.6) than in the placebo group (from 5.3 to 4.2), although the difference between groups was not significant (p = 0.06). The 95% confidence interval for the difference in slopes of regression lines obtained from trimonthly manual muscle tests on all subjects was markedly asymmetric in favor of the diltiazem group, but this difference was also not significant. There was less deterioration of functional activity of lower extremities in the diltiazem-treated group, when beginning and end values were analyzed (p = 0.03). However, the difference in slopes of regression lines obtained from trimonthly determinations was nonsignificant. Similarly, the beginning versus end comparisons of systolic and diastolic blood pressure showed a significantly (p less than 0.05) smaller elevation of blood pressure in the diltiazem-treated group, but no difference was observed when the slopes of all values were analyzed. All other clinical and laboratory variables were unaffected by diltiazem treatment. The findings in manual muscle tests and functional activity suggest a beneficial trend with chronic diltiazem treatment in DMD.