Zinc has generally been administered by the oral route in studies of prevention or treatment of the common cold. The purpose of these studies was to evaluate the effectiveness of intranasal zinc gluconate for prevention of experimental rhinovirus infection and illness. Ninety-one volunteers, 41 treated with active medication and 50 treated with placebo, received study medication for 3 days, were inoculated with rhinovirus, and then were treated with study medication for an additional 6 days. Rhinovirus infection was documented in 37 (74%) of the 50 placebo-treated volunteers and in 32 (78%) of the 41 volunteers treated with active medication. Zinc treatment had no effect on total symptom score, rhinorrhea, nasal obstruction, or the proportion of infected volunteers who developed clinical colds. These data do not support a role for intranasal zinc gluconate for prevention or treatment of the common cold.