Flecainide acetate has been shown to have use-dependent properties. The use-dependent properties of flecainide were evaluated in 20 patients (13 men and 7 women, mean age 32 +/- 11 years) with accessory atrioventricular connections. Twenty to 30 stimulus drive trains were introduced in either the atrium or ventricle at progressively faster rates. The range of cycle lengths over which anterograde and retrograde conduction block occurred in the accessory pathway was assessed in the drug-free state and after oral loading with flecainide acetate. The block cycle length index was defined as the shortest cycle length during which 1:1 conduction was maintained in the accessory pathway minus the longest cycle length during which block in the accessory pathway occurred on the second paced beat. In the drug-free state, the (mean +/- SD) anterograde and retrograde block cycle length indexes were 20 +/- 12 and 20 +/- 9 ms, respectively. After flecainide therapy, the anterograde and retrograde block cycle length indexes increased to 80 +/- 33 and 65 +/- 29 ms, respectively (p = 0.002 compared with the drug-free state). The block cycle length index did not correlate with serum flecainide levels, but did correlate with other electrophysiologic markers of drug effect on accessory pathway conduction. The change in the block cycle length index demonstrates that flecainide has a progressive effect on accessory pathway conduction at more rapid rates, consistent with its in vitro use-dependent properties. This index is an excellent marker of drug efficacy.