Côte d'Ivoire is an endemic area for Plasmodium falciparum malaria, with perennial transmission in the southern forest and seasonal transmission in the northern savannah. Change of first-line treatment of uncomplicated malaria to artemisinin-combination therapy (ACT) is widespread in the country as elsewhere in Africa. The present study was conducted to assess the in vitro response of Plasmodium falciparum to antimalarial drugs currently used in the country (chloroquine, artemisinin and dihydroartemisinin) and new drugs that could be used in the near future (pyronaridine) and to analyse the pattern of cross-resistance between these drugs. The standard in vitro drug sensitivity microtechnique recommended by the World Health Organization was used to assess the sensitivity of Plasmodium falciparum isolates collected in Abidjan (Côte d'Ivoire) between April and December 2006. Of 128 in vitro tests performed, 112 (87.5%) were successful. Among them, 32, 27, 25, and 28 P. falciparum isolates grew satisfactorily and yield interpretable results for chloroquine, pyronaridine, artemisinin, and dihydroartemisinin respectively. The proportions of resistant isolates were 56.2% for chloroquine, 48% for pyronaridine, 36% for artemisinin and 3.6% for dihydroartemisinin. The most potent drug was dihydroartemisinin with a geometric mean IC50 of 2.72 nM ranged from 1.45 to 3.99 nM. No multi-resistant isolates (showing resistance to more than three drugs) were found. A positive correlation was found between the IC50 values for the following drugs: chloroquine and pyronaridine (r=0.45), pyronaridine and dihydroartemisinin (r=0.40), chloroquine and artemisinin (r=0.68), artemisinin and dihydroartemisinin (r=0.62). Data suggested cross-resistance between these drugs and warrant an improved surveillance programme for drug resistance to malaria in Côte d'Ivoire.