Hawaiian medicinal plants commonly used for the treatment of a variety of infections were screened for antiviral activity against human immunodeficiency virus type 1 (HIV-1). Sixty-one extracts derived from seventeen plants were tested for selective viral growth inhibition using the LAI (HTLV-III B) isolate. The greatest degree of antiviral activity was observed with aqueous extracts made from the bark of Eugenia malaccensis (L.) and the leaves of Pluchea indica (Less.) which had antiviral selectivity indices (50% cytotoxic concentration/50% effective antiviral concentration) of 109 and 94, respectively. These and other extracts conferred 100% cell protection against viral cytopathic effect when compared with control samples. Methanol and water extracts made from the Pipturus albidus (Gray) leaves and bark also achieved a high selective inhibition of virus replication with very low cytotoxicity. Plant extracts made from Aleurites moluccana (Willd.), Psychotria hawaiiensis (Gray), Clermontia aborescens (Mann), and Scaevola sericea (Forst.) also showed antiviral activity. These data provide a rationale for the characterization of antiviral natural products from these plants and related plant species.