To investigate host factors affecting the delay of reappearance of malaria parasites after radical treatment, a study was undertaken in Dielmo, Senegal, an area of intense perennial malaria transmission. A 7-day course of quinine was administered to 173 asymptomatic persons from 1 to 85 years of age and reappearance of malaria parasites in the peripheral blood was monitored weekly for 14 weeks. Additional thick blood films were made in case of fever as part of a daily clinical surveillance. The median times before reappearance of Plasmodium falciparum were 22, 39, and 53 days among persons 1-6, 7-14, and > or = 15 years of age, respectively (P < 0.0001). Multivariate analysis indicated that the daily rate of reappearance of P. falciparum was 2.2 (95% confidence interval [CI] = 1.2-4.5) times lower in sickle cell trait carriers than in AA individuals, and 1.5 (95% CI = 1.1-2.1) times lower in bed nets users than in non-users. The risk ratio for the daily risk of reappearance was significantly related to the level of parasitemia before treatment. No influence of glucose-6-phosphate dehydrogenase deficiency, HLA-B53, and DR13 were observed. Findings show that monitoring during a few weeks the reappearance of malaria parasites after treatment among a small cohort of individuals naturally exposed to malaria is relevant for investigating host resistance factors. This suggest that small, low-cost, field trials may be very informative on the potential of new malaria vaccine candidates.