Feline malignant lymphoma occurs commonly in domestic cats and may serve as a model for non-Hodgkin's lymphoma in humans. Several studies have suggested that smoking may increase the risk of non-Hodgkin's lymphoma. To evaluate whether exposure to household environmental tobacco smoke (ETS) may increase the risk of feline malignant lymphoma, the authors conducted a case-control study of this relation in 80 cats with malignant lymphoma and 114 controls with renal disease diagnosed at a large Massachusetts veterinary teaching hospital between 1993 and 2000. Owners of all subjects were sent a questionnaire inquiring about the level of smoking in the household 2 years prior to diagnosis. After adjustment for age and other factors, the relative risk of malignant lymphoma for cats with any household ETS exposure was 2.4 (95 percent confidence interval: 1.2, 4.5). Risk increased with both duration and quantity of exposure, with evidence of a linear trend. Cats with 5 or more years of ETS exposure had a relative risk of 3.2 (95 percent confidence interval: 1.5, 6.9; p for trend = 0.003) compared with those in nonsmoking households. These findings suggest that passive smoking may increase the risk of malignant lymphoma in cats and that further study of this relation in humans is warranted.