The purpose of this study was to evalute the antimalarial action of a new tetracycline analogue, minocycline, which is more potent and has a broader antibacterial spectrum than tetracycline. The study was conducted in an area endemic for chloroquine-resistant falciparum malaria. Acutely ill residents infected with P. falciparum were alternately assigned to one of two treatment groups. Subjects in one group were given 540 mg of quinine base, thrice daily for 3 days followed by 100 mg of minocycline, twice daily for 7 days. Subjects in the other group were given a similar course of quinine followed by 250 mg of tetracycline, 4 times daily for 10 days. Presumptive radical cures were achieved in all 29 patients treated with quinine-tetracycline and in 27 of 28 treated with quinine-minocycline. No significant toxic side-effects were observed. Although both treatments were highly effective, further studies are warranted to determine the optimal duration and dosage of minocycline and its potential human toxicity.