The susceptibility of Plasmodium falciparum to chloroquine, quinine, mefloquine and halofantrine was investigated in the Central Province of Papua New Guinea between March 1995 and September 1996, when chloroquine resistance was widely present in the country. The standard World Health Organization in vitro microtest methodology was used in the study. Of the 30 isolates tested for chloroquine susceptibility all were resistant to chloroquine with median IC50 of 1.15 mumol/l (range 0.54 to 4.24), indicating a high prevalence and degree of resistance. Three isolates each for quinine (3/31) and halofantrine (3/28) showed resistance at concentrations of 51.2 mumol/l and 10 nM respectively, while all 31 isolates tested for mefloquine were fully susceptible. The comparative analysis of median IC50 values between isolates resistant and susceptible to chloroquine showed chloroquine-resistant isolates to be less susceptible to quinine and halofantrine while fully susceptible to mefloquine. It seems that the evolution of chloroquine resistance together with increased use of quinine treatment of P. falciparum malaria may increase the risk of emergence of quinine resistance and possibly of halofantrine resistance as well. The development of mefloquine resistance, however, is independent of chloroquine resistance.