The recent reappearance of Plasmodium falciparum in the central highland plateaux of Madagascar has led to an important increase in both morbidity and mortality in the population. To understand the phenomena that originated this outbreak, and to evaluate the clinical and biological reactions of the population, we conducted entomological surveys during the whole malaria transmission season of 1988. In parallel, 41 individuals presenting with a malaria attack in January were given a curative antimalarial treatment and were followed weekly for 20 weeks, until the end of the transmission season, in June. During the follow-up, individuals presenting with a clinical malaria attack or with a parasite density above 5000 per mm3 of blood were again given antimalarial treatment. Overall, individuals presented with an average of 5.6 thick blood smears positive for P. falciparum, and 1.4 malaria attacks requiring treatment. Plasmodium falciparum prevalence rates gradually increased to 53.8% in April, one to two months after the observed peak of transmission, then decreased to 15.4% at the end of follow-up. The proportion of P. falciparum infections with clinical symptoms did not follow a similar temporal evolution and was significantly lower than at enrollment. Splenic rates gradually decreased from 29.3-2.6%, while anti-P. falciparum and anti-Pfl55/RESA antibodies increased. For the whole transmission season individuals experienced a mean 1.5 infective bites; the malaria vectors were Anopheles gambiae s. 1 and An. funestus. This study demonstrates that, in this population newly exposed to P. falciparum infections, almost all sporozoite inoculations lead to blood parasite infection requiring treatment.(ABSTRACT TRUNCATED AT 250 WORDS)