Between 1982 and 1984 a regimen consisting of quinine and tetracycline was routinely used in Thailand to treat outpatients with microscopically confirmed falciparum malaria. Due to compliance problems associated with the 7-day multiple-dose regimen, there was a recrudescence rate of approximately 30%. Studies carried out in 1982 and 1984 in four areas of Thailand indicated that there was a significant decrease in the sensitivity of Plasmodium falciparum to quinine. A significant, though less marked, reduction in the sensitivity of P. falciparum to the structurally related drug mefloquine was also observed, although this compound was not operationally deployed in Thailand before 1985. These findings emphasize the need to replace the long multiple-dose quinine regimen by an effective, acceptable, single-dose treatment.