Two very distinct malaria zones can be found within Simbu Province. The north of the province is characterized by the absence or very low level of local malaria transmission, but there is a considerable risk of epidemics prevalent in the lower-lying parts. During non-epidemic periods, parasite prevalence was usually under 5%, with similar frequencies for Plasmodium falciparum and P. vivax (47% each), and malaria was an only minor source of febrile illness. During epidemics, however, 13-36% of people were infected, predominantly with P. falciparum (64%), and high levels of severe morbidity were present. In south Simbu malaria is clearly endemic with an overall prevalence of 35%, combined with a strong age-dependence of infections, low haemoglobin levels, high rates of enlarged spleen and moderate to severe anaemia (haemoglobin level < 7.5 g/dl) in children. The malaria epidemiology in south Simbu is thus more similar to the lowlands than to other highlands areas. Epidemic prevention, surveillance and response in the north, and bednet distribution and strengthening of curative services in the south, are therefore the priorities for malaria control in Simbu Province.