The incidence of non-Hodgkin's lymphoma (NHL) is increased in many counties in eastern Nebraska. Histologic analysis has revealed a twofold increase in the clinically aggressive, diffuse large cell subtype of NHL. To investigate the possible association between NHL and agricultural exposures, a population-based case-control study was conducted in eastern Nebraska in 1985. Telephone interviews were conducted with 201 men having histologically confirmed NHL and 725 controls. Among men, the use of the herbicide 2,4-D was associated with a 50% increased risk of NHL (OR 1.5, 95% CI 0.9, 2.4). Personal exposure to 2,4-D more than 20 days per year increased the risk threefold (OR 3.3, 95% CI 0.5, 22.1). Several classes of insecticides were also associated with increased risk: organophosphates (OR 1.9, 95% CI 1.1, 3.1), carbamates (OR 1.8, 95% CI 1.0, 3.2), and chlorinated hydrocarbons (OR 1.4, 95% CI 0.8, 2.3). As a result of intense agrichemical use, extensive contamination of shallow groundwater by nitrate and atrazine has also occurred in eastern Nebraska. A twofold increased incidence of NHL is present in counties with greater than 20% of the wells contaminated by nitrate (greater than 10 ppm) and in counties with intense fertilizer use. These findings suggest that NHL in eastern Nebraska may be related to the use of pesticides and nitrogen fertilizers.