Tetracycline was administered to 22 volunteers infected with chloroquine-resistant Plasmodium falciparum (either the Camp. or Marks strain) and to seven volunteers infected with chloroquine-sensitive P. falciparum (Uganda I strain). Volunteers had become partially immune to their infections before they received 250 mg of tetracycline hydrochloride, given orally every 6 hours for 3¼, 5, or 7 days. Clearance of asexual parasites, although slow (mean, 4.5 days), was observed after each regimen of medication. In febrile patients, fever and symptoms usually subsided more slowly. After treatment with tetracycline for 3¼ days, initial clearance of patent parasitemia preceded recrudescence of asexual parasites in ll three patients infected with chloroquine-resistant malaria. Treatment for 5 days effected radical cure in all five infections with the Camp. strain, but parasitemia recurred in the single infection with the Ugandan strain. Administration of tetracycline for 7 days effected radical cure in all 10 persons infected with the Camp. strain, in 3 of 4 persons infected with the Marks strain, and in all 6 persons infected with the Uganda I strain. Tetracycline seemed to exert no effect against gametocytes. The findings indicate that tetracycline, although not recommended for treatment of acute episodes of malaria, may be of potential value, as an adjunctive agent, in achieving radical cure of drug-resistant infections of P. falciparum.