To determine the duration and complexity of naturally acquired Plasmodium falciparum infections in small children, a longitudinal cohort study of 143 newborns was conducted in coastal Ghana. On average, children experienced 2 episodes of infection in their first 2 years of life, the median duration of an asymptomatic infection was <4 weeks, and estimates of the mean number of parasite genotypes per infection were 1.15-2.28. Nevertheless, 40% of the children experienced infections lasting </=12 weeks, and both the duration and complexity of infections increased with age. The longest period of continual infection was 64 weeks, and the maximum persistence of a single parasite genotype was 40 weeks. Thus, malaria infections in infants <5 months old tend to be asymptomatic and rapidly cleared; persistent asymptomatic parasitemia is more common in children >5 months old. The ability of very young children to clear or control malaria infections indicates the presence of effective innate or immune antiparasite mechanisms.