Quinine has been an effective drug for severe chloroquine-resistant falciparum malaria. However, there has been a decline in the sensitivity of Plasmodium falciparum to quinine. In 1978-1979 the cure rate was 94% compared to 86% in 1979-1980 and 76% in 1980-1981. The combination of quinine and tetracycline has improved the cure rate to 95-100%. However, the mechanism responsible for this has not been identified. We have compared plasma quinine levels on day 2, day 5 and day 7 (before and at 2 hours after dosing) in twenty-one patients with acute falciparum malaria who were treated with quinine alone (8 patients) or quinine in combination with tetracycline (8 patients) or quinine with tetracycline and primaquine (5 patients). All patients who received combination of quinine and tetracycline with or without primaquine responded well to the treatment with no recrudescence. Two patients who were treated with quinine alone had RI responses. Plasma quinine concentrations from the quinine alone group were significantly lower than those obtained from combination groups on days 2, 5 and 7. The minimal plasma quinine levels from quinine alone group were all lower than MIC, ie below 10 micrograms/ml while those obtained from the combination group were higher than MIC for 7 days. The results from the present study suggest that tetracycline has influence on the maintenance of plasma quinine levels above MIC throughout the treatment period. Therefore, this must be one possible explanation for the better cure rate.