In the United States, non-Hodgkin's lymphoma incidence rates have risen 3 percent per year for four decades, and non-Hodgkin's lymphoma mortality 1.6 percent compared with 0.2 percent for all cancers combined. An analysis of trends in both sexes and around the world suggests that the rise may be due to an etiologic agent(s) that has become increasingly prevalent in the general environment. Based on studies showing increased risk of non-Hodgkin's lymphoma among farmers exposed to pesticides, we are investigating risk that may be associated with environmental pesticide exposures. We conducted a multi-disciplinary case-control study of non-Hodgkin's lymphoma in 4 SEER areas (1998-2000). We measured pesticides in household dusts, serum samples, and tap water. We collected questionnaire data on numerous exposures including pesticides residential and other, occupation, diet, tobacco, sunlight, hairdyes, cell phones, and alcohol. We collected blood or buccal cells to measure viral exposures (including HCV and SV40) and common genetic variants in important pathways (including immune function and oxidative stress). We preceeded the case-control study with pilot studies, and are pursuing observations in InterLymph and in cohort studies.