The in vitro response of Plasmodium falciparum to mefloquine was assessed using WHO standard test kits. Mefloquine resistance at concentrations greater than or equal to 16 pmol/well (3.2 microM) was observed in 15.2% (5/33) and 3.6% (1/28) of the isolates from Lubwe and Kalene respectively. 48.5% of the isolates from Lubwe and 21.4% of those from Kalene had minimum inhibitory concentrations (MICs) greater than or equal to 3.2 microM. Mefloquine effective concentration 99% (EC99) values were 2.16 microM for Lubwe and 1.19 microM for Kalene. Cross-resistance between mefloquine and chloroquine was recorded in 4 of the resistant isolates from Lubwe. Mefloquine effective concentrations 99% (EC99) observed for these isolates ranged from 2.8 microM to 7.69 microM. The sensitivity pattern of mefloquine at both localities seemed to follow that of chloroquine. Although mefloquine is not yet in use in the study area, some P. falciparum isolates have shown the capacity to develop resistance in vitro. These findings might have an important bearing on the usefulness of mefloquine in its eventual introduction into the area for clinical use.