Background: Historically, prostate cancer mortality rates have been elevated in the U.S. Northern Plains states. The purpose of this study was to investigate possible contributing factors, especially whether there was any association with crop patterns. Methods: Prostate cancer mortality rates (1950-2000) in four northern plains states (MN, MT, ND, and SD) were compared to rates for 46 other U.S. states. Within the four states, county rates in urban, less urban, and rural areas also were compared. For additional analysis, urban counties and counties with <10% of county area in crops were excluded. The average percent of county area in total cropland 1930-1950 and 1954-1974 was estimated. Using Poisson regression, we investigated whether the average percentage of county area in total cropland, 1930-1950 and 1954-1974, was associated with prostate cancer mortality rates, 1975-2000, respectively. Poisson regression analyses were also used to evaluate associations between rates and major crops, which included spring and durum wheat, winter wheat, corn, and other crops. Population centroids of the Census 2000 block groups were used to estimate the percentage of males aged 35 and older residing in close proximity to small grains crops. Results: Mortality rates were higher in rural compared to urban counties in 1950-2000 (rate ratio [RR]=1.032; 95% CI=1.001-1.063). Rates in 1950-1974 were significantly associated with production of corn and other crops in 1930-1950 (corn: RR per 10% increase=1.033, 95% CI=1.012-1.054; other crops: RR=1.042, 95% CI=1.021-1.063). Mortality rates in 1975-2000 were significantly associated with spring and durum wheat production in 1954-1974 (RR per 10% increase=1.042, 95% CI=1.017-1.067). Prostate cancer mortality rates increased as the percentage of population living within 500 m of small grains crops increased. Conclusions: Epidemiologic studies to evaluate agricultural practices are warranted to further evaluate the observed associations.