The efficacy of oral WIN 54954 for the prevention of rhinovirus infection and illness was tested in two randomized, double-blinded, placebo-controlled volunteer challenge studies. Volunteers were inoculated with rhinovirus type 39 (MIC of WIN 54954, 0.17 microgram/ml) or rhinovirus type 23 (MIC, 0.016 microgram/ml). The volunteers received two doses of drug (600 mg per dose) or placebo on the first day; this was followed by three doses on each of the subsequent 5 days. All volunteers were challenged with virus after the third dose of study drug. No significant antiviral or clinical effect was detected in either study. Pharmacokinetic studies revealed that on the last day of drug administration, 38 of 39 (97%) volunteers had trough levels of WIN 54954 in plasma greater than the MIC for the respective virus. Nasal wash specimens collected on the same day revealed a detectable level in only 6 of 24 (25%) volunteers at the peak (range, 6 to 24 ng/ml) and in only 2 of 14 (14%) volunteers at the trough (range, 6 and 7 ng/ml). These results suggest that the lack of efficacy of WIN 54954 against rhinovirus may be related to an inability to deliver sufficient drug to the site of viral infection.