Multidrug-resistant Plasmodium falciparum is widespread in Cambodia. The in vitro susceptibilities of 14 Cambodian isolates to chloroquine, quinine, mefloquine, halofantrine, pyrimethamine, cycloguanil, pyronaridine, artemisinin, arteether, artemether and artelinate were studied using a semi-microtest on day 0 and after 15-30 days of culture. The culture-adapted isolates were all resistant to chloroquine, pyrimethamine and cycloguanil. The susceptibility to quinine was generally low. Three isolates were resistant to mefloquine. A comparison of susceptibility to cycloguanil, quinine, and mefloquine prior to and after culture adaptation showed a trend toward a higher resistance level in some isolates. Halofantrine, pyronaridine and artemisinin derivatives were highly active against the multidrug-resistant Cambodian isolates, with very similar 50% inhibitory concentrations (IC50). These results confirm the presence of multidrug-resistant P. falciparum isolates in Cambodia and indicate that quinine- and mefloquine-resistant populations of the parasite may already exist in the field. The high in vitro activities of halofantrine, pyronaridine and artemisinin derivatives indicate their potential usefulness for the treatment of multidrug-resistant malaria.