The cutaneous application of antiviral agents was studied by iontophoresis, a process that increases penetration of most drugs 20- to 60-fold. Twenty-seven subjects with vesicular orolabial herpes were treated one time in a double-blind, placebo-controlled clinical study: nine received vidarabine monophosphate (ara-AMP), nine received acyclovir (ACV), and nine received NaCl. Ara-AMP-treated lesions yielded lower titers of virus after 24 hr compared with lesions treated with NaCl or ACV (P less than .05). Ara-AMP significantly decreased the duration of shedding of virus (P less than .05) and time to dry crust (P less than .05) compared with the other two agents. There was a trend toward decreased healing time after ara-AMP treatment.