ABSTRACT: BACKGROUND: Malaria due to Plasmodium falciparum is the leading cause of morbidity and mortality in Tanzania. According to health statistics, malaria accounts for about 30% and 15% of hospital admissions and deaths, respectively. The risk of P. falciparum infection varies across the country. This study describes the spatial variation and socio-economic determinants of P. falciparum infection in northeastern Tanzania. METHODS: The study was conducted in 14 villages located in highland, lowland and urban areas of Korogwe district. Four cross-sectional malaria surveys involving individuals aged 0-19 years were conducted during short (Nov-Dec) and long (May-Jun) rainy seasons from November 2005 to June 2007. Household socio-economic status (SES) data were collected between Jan-April 2006 and household's geographical positions were collected using hand-held geographical positioning system (GPS) unit. The effects of risk factors were determined using generalized estimating equation and spatial risk of P. falciparum infection was modelled using a kernel (non-parametric) method. RESULTS: There was a significant spatial variation of P. falciparum infection, and urban areas were at lower risk. Adjusting for covariates, high risk of P. falciparum infection was identified in rural areas of lowland and highland. Bed net coverage levels were independently associated with reduced risk of P. falciparum by 19.1% (95%CI: 8.9-28.2, p