Although maize pollen is known to provide nutrition for larval anopheline mosquitoes, the epidemiologic relationship between maize agriculture and malaria transmission has never been defined. To determine whether recent changes in malaria transmission in Ethiopia might be linked to the spread of maize as a commercial crop, we compared malaria transmission and maize cultivation intensity in 21 villages in the Bure District of northwestern Ethiopia where maize cultivation has recently expanded. The cumulative incidence in high maize cultivation areas was 9.5 times higher than in areas with less maize. A chi-square goodness-of-fit test results showed that malaria cases were not distributed evenly among categories of maize cultivation intensity, (?2 = 1,578, P < 0.001). A Poisson regression suggested that the intensity of maize cultivation, controlled for differences in elevation between sites, was positively and significantly correlated with malaria incidence. Thus, the intensity of maize cultivation was associated with exacerbated human risk of malaria in Bure.