The authors evaluated the incidence of cancer among pesticide applicators with exposure to alachlor in the Agricultural Health Study, a prospective cohort study of licensed pesticide applicators in Iowa and North Carolina. A total of 49,980 pesticide applicators are included in this analysis; 26,510 applicators (53%) reported use of alachlor on the enrollment questionnaire. Detailed pesticide exposure and other information were obtained from a self-administered questionnaire completed at the time of enrollment (1993-1997). Poisson regression analysis was used to evaluate the exposure-response relations between alachlor and cancer incidence controlled for the effects of potential confounding factors. A total of 1,466 incident malignant neoplasms were diagnosed during the study period, 1993-2000. Among alachlor-exposed applicators, the authors found a significant increasing trend for incidence of all lymphohematopoietic cancers associated with lifetime exposure-days (p for trend = 0.02) and intensity-weighted exposure-days (p for trend = 0.03) to alachlor. The risks of leukemia (rate ratio = 2.83, 95% confidence interval: 0.74, 10.9) and multiple myeloma (rate ratio = 5.66, 95% confidence interval: 0.70, 45.7) were increased among applicators in the highest alachlor exposure category. Our findings suggest a possible association between alachlor application and incidence of lymphohematopoietic cancers among applicators in the Agricultural Health Study.