A randomized, double-blind study assessed the efficacy and safety of pleconaril, a novel antiviral drug with broad-spectrum activity against picornaviruses, in the treatment of 33 adults with an experimentally induced viral respiratory infection. Subjects received either pleconaril 200 mg twice daily (initial dose of 400 mg) or placebo for 7 days. Fourteen hours after receiving the initial dose of either pleconaril or placebo, subjects were inoculated intranasally with 100 plaque-forming units of coxsackievirus A21. Results revealed statistically significant reductions in viral shedding in nasal secretions (P<.001), nasal mucus production (P=.004), and total respiratory illness symptom scores (P=.013) in pleconaril-treated as compared with placebo-treated subjects. The most common adverse events were nausea and abdominal pain. These data support the safety and efficacy of pleconaril in decreasing the signs and symptoms and viral shedding associated with a viral respiratory infection.