Severe immune dysfunction is an established risk factor of lymphoma, but the role of moderate alterations of immunity is not clear and prospective investigations are needed. We examined several immune-related disorders and medications in relation to non-Hodgkin lymphoma (NHL) in the Multiethnic Cohort. Over 215,000 subjects of African American, Caucasian, Japanese American, Latino and Native Hawaiian ancestry aged 45-75 years completed a questionnaire, including information on medical history, in 1993-1996. After exclusions, we performed Cox regression among 193,050 cohort members including 939 incident NHL cases while adjusting for sex, age, ethnicity, education, body mass index and alcohol intake. Self-reported diabetes was not associated with NHL overall, but was positively associated with risk among Japanese Americans [hazard ratio (HR) = 1.55; 95% confidence interval (CI): 1.10-2.17]. Participants with a history of blood transfusion were at increased risk with HR = 1.39 (95% CI: 1.06-1.84) in men and HR = 1.22 (95% CI: 0.94-1.58) in women, especially for the diffuse large B-cell lymphoma subtype. History of asthma or other allergies was associated with elevated risk only among Latinos (HR = 1.46; 95% CI: 1.07-2.00) who also showed a significant relation between current use of antihistamines and NHL (HR = 1.80; 95% CI: 1.09-2.97). Use of nonsteroidal anti-inflammatory drugs was not associated with NHL. Our findings from this large prospective study support a moderate risk for NHL related to blood transfusions, current long-term antihistamine use and diabetes, but the associations were limited to certain ethnic groups and require further replications.