The effects of rimantadine on dengue virus replication were examined in a variety of tissue culture systems. The growth of dengue virus type 2 in human peripheral blood leukocytes (PBL) was completely suppressed when rimantadine was included in the culture medium at a concentration of 25 µg/ml. Similarly, rimantadine caused a significant inhibition of dengue virus replication in cultures of rhesus monkey PBL. Addition of drug into virus-infected LLC-MK2 cell cultures caused a decrease in the production of all four types of dengue virus. Maximal inhibition of dengue virus replication by rimantadine was observed when the drug was added immediately following the viral adsorption period. Rimantadine did not induce any cytopathic effects on either LLC-MK2 cells or PBL at concentrations less than 75 µg/ml. These findings demonstrate that rimantadine is an effective inhibitor of dengue virus replication in vitro, and indicate a need for further examination of the efficacy of rimantadine against severe dengue virus disease.