The electrophysiologic effects and safety of diltiazem administered either intravenously or orally were studied in 14 patients with Wolff-Parkinson-White syndrome during orthodromic reentrant tachycardia and atrial fibrillation (AF). Anterograde and retrograde effective refractory periods of the accessory pathway did not change significantly from baseline during either i.v. or oral administration. Administration by either route prevented induction of sustained reentrant tachycardia in 8 patients. In 6 patients, the reentrant tachycardia was either nonsustained (2 patients) or sustained at much slower rates than the baseline rates (mean +/- standard deviation, baseline, 290 +/- 41 ms; i.v., 355 +/- 40 ms [p less than 0.001]; and oral, 377 +/- 33 ms [p less than 0.001]). In these patients anterograde atrioventricular conduction was prolonged significantly from the mean baseline value of 163 +/- 36 ms to 212 +/- 35 ms with i.v. administration (p less than 0.005) and 225 +/- 33 ms with oral administration (p less than 0.005). Retrograde conduction via the accessory pathway did not change significantly after administration of diltiazem. The shortest preexcited RR intervals during AF were significantly reduced during i.v. but not during oral administration: control, 327 +/- 47 ms; i.v., 270 +/- 28 ms (p less than 0.001); and oral, 323 +/- 44 ms (difference not significant). In 5 patients AF was sustained for a mean of 20 minutes after i.v. and for 12 minutes after oral administration (p less than 0.20), compared with a baseline mean value of 0.83 minute.(ABSTRACT TRUNCATED AT 250 WORDS)