Anemia during childhood remains a major public health challenge in sub-Saharan Africa. To determine the prevalence of and the main risk factors for anemia in young children, we conducted a longitudinal survey in Ebolowa in southern Cameroon. Children were enrolled in two cohorts and followed during a three-year period: the first cohort was composed of 122 children from 0 to 36 months of age and the second cohort was composed of 84 children from 24 to 60 months of age. The two cohorts were followed weekly for symptomatic malaria, monthly for both symptomatic and asymptomatic malaria, and every six months for hematologic data; the children were grouped into six-month age groups. The prevalence of anemia (hemoglobin [Hb] level < 11 g/dl) was the highest in the six-month-old age group (47%) and the age-related evolution clearly showed a decrease in the prevalence from three years of age. Thus, 42% of the children less than three years of age were anemic, while 21% of the children between three and five years of age were anemic. The lowest mean +/- SD Hb content (10.7 +/- 2.1 g/dl) was observed in the six-month-old children and a regular improvement in the Hb level occurred from six months to three years of age. A stabilization was observed at a level of approximately 12 g/dl. At any age, there was no difference in mean Hb levels between children with AS and AA Hb genotypes. Hookworm infection was diagnosed in two children in the study population. Results of a multivariate analysis showed that placental malaria infection was the strongest risk factor for anemia in the six-month-old children (odds ratio [OR] = 3.6; 95% confidence interval [CI] = 1.1-12.3) and was independent of the frequency of parasitemia, parasitemia at the time of Hb measurement, or microcytosis. In the one-year-old age group, microcytosis was a significant factor related to anemia (OR = 2.8, 95% CI = 1-7.8) pointing out the role of iron deficiency at this age. Parasitemia at the time of Hb measurement was significantly associated with anemia in all age groups (except in 54- and 60-month-old groups). Strategies to decrease the prevalence of anemia in young children in southern Cameroon should include chemoprophylaxis for pregnant women, prevention of acquired malaria infection in both pregnancy and infancy, and prevention of nutritional iron deficiency.