The prophylactic efficacy of the broad-spectrum antiviral nucleoside analog ribavirin against flavivirus infection in non-human primates was investigated in a blinded, placebo-controlled study of rhesus monkeys infected with dengue virus. Both placebo- and ribavirin-treated monkeys developed viremia, as measured by direct plaque assay on Aedes albopictus C6/36 cells. Peak viremia occurred between days 3 and 9 after infection. No significant differences in time of onset, duration, or level of viremia were observed between placebo- and ribavirin-treated monkeys. Ribavirin induced predictable and reversible anemia and thrombocytosis. Serum ribavirin reached maximum levels of 30 microM by day 4, which approximates the in vitro minimum inhibitory concentration for dengue virus. Ribavirin appeared ineffective as a prophylactic drug for dengue type 1 viral infection, as evaluated by the magnitude of viremia in this monkey model.