Detection of Plasmodium falciparum by polymerase chain reaction (PCR) was evaluated in 33 P. falciparum-infected patients with two different amplification systems over 5-7 days of curative treatment. In the K1-14 system, a P. falciparum DNA fragment of 206 bp was detected, and in the circumsporozoite (CS) system, a fragment of 800 bp was detected. The K1-14 and CS systems identified 95% and 93%, respectively, of 103 microscopically identified specimens; both systems detected as few as 11 parasites/microliters among these specimens. Specimens from 20 smear- and history-negative controls were all negative by both PCR systems. The K1-14 and CS systems detected P. falciparum DNA in 53% and 20%, respectively, of blood films collected on the first day and 3% and 0 of the blood films collected on the fourth day after reversion to microscopic negative. The simultaneous use of two independent PCR systems to monitor patients during curative treatment of P. falciparum infections convincingly demonstrated that P. falciparum DNA was present transiently in the blood of infected patients at a time when the parasite could no longer be detected microscopically.