Tetracycline hydrochloride was evaluated in asymptomatic and acutely ill subjects naturally infected with chloroquine resistant strains of Plasmodium falciparum. Sixteen asymptomatic subjects of whom eight had recently experienced chloroquine treatment failures received 250 mg of tetracycline hydrochloride, four times daily for ten days. A presumptive radical cure was demonstrated in 12. In the other four, treatment was discontinued within 72 hours because of symptomatic development. Acutely ill subjects were assigned to one of two treatment groups. One group received 640 mg of quinine sulfate, three times daily for three days, followed by 250 mg of tetracycline hydrochloride, four times daily for ten days. The other group received a similar course of quinine followed by a conventional course of chloroquine. A presumptive radical cure was demonstrated in 29 of 30 treated with the quinine-tetracycline regimen, and in 15 of 36 treated with the quinine-chloroquine regimen.