Falciparum malaria is a major cause of morbidity and mortality among tourists returning from endemic areas. Treatment of infected travellers is frequently standardised, and resistance tests are rarely done as they are difficult to perform and interpret. In vitro tests of resistance to chloroquine, mefloquine, quinine, halofantrine, tetracycline, and sulfadoxine/pyrimethamine were performed on Plasmodium falciparum isolates obtained from 52 German travellers returning from malarious areas in sub-Saharan Africa. All patients were treated successfully with a standard dose of mefloquine. No in vivo resistance was observed. Although 20 (38.5%) isolates showed no signs of in vitro resistance, the remaining 32 (61.5%) were resistant to at least one of the tested antimalarial agents. Of these 32 isolates, 11 were multiresistant. Resistance to chloroquine was most frequently observed (55.8%), followed by sulfadoxine/pyrimethamine (11.5%), mefloquine (9.6%), quinine (3.8%), and halofantrine (1.9%). In vitro resistance to tetracycline was not detected in this study group. Treatment of falciparum malaria without resistance testing appears to be effective in most cases, but possible therapeutic failure due to emerging drug resistance should be kept in mind.