A randomized, open study of high-dose ciprofloxacin (750 mg every 12 h) in uncomplicated falciparum malaria was conducted in Thailand. No patient completed the planned 1-week treatment course. Because of rising parasitemia (threefold higher at 36 h than on admission) and deterioration of clinical status, three individuals required quinine treatment 36 h after commencing ciprofloxacin; a fourth was given quinine at 54 h. The study was terminated early for safety reasons after only four ciprofloxacin and four control patients had been enrolled. Ciprofloxacin was well absorbed and efficiently entered erythrocytes; median plasma and red cell concentrations 90 min after the first dose were 4.0 (range, 3.7-6.8) and 5.1 (3.8-6.0) micrograms/ml, respectively. However, 50% inhibition of parasite growth in vitro required 6.6 micrograms/ml, (5.6-9.6). Ciprofloxacin should not be used alone to treat chloroquine-resistant falciparum malaria.