Acute myelogenous leukemia (AML) is a heterogeneous disease with distinct histologic subtypes likely to have distinct risk factors. The authors examined smoking and the risk of adult AML by French-American-British (FAB) subtype in a Los Angeles County, California, population-based case-control study of 412 cases diagnosed between 1987 and 1994 and 412 matched controls. Consistent with previous studies, smoking was not a substantial risk factor for AML overall (odds ratio (OR) = 1.2, 95% confidence interval (CI): 0.9, 1.6). However, increased risk was observed for FAB subtype M2 (OR = 2.3, 95% CI: 1.1, 4.4), particularly for subjects aged 60-75 years (OR = 3.3, 95% CI: 1.1, 10.0). For M2, significant dose-response was associated with total years smoked (p = 0.02), cigarettes per day (p = 0.007), and product filter status (filtered vs. nonfiltered; p = 0.03). The authors estimate that 42% (standard error = 13%) of M2 cases are attributable to smoking. There were no or weak associations between smoking and increased AML risk for other FAB subtypes. The finding by this study of an association between smoking and FAB subtype M2 confirms a previously published report and suggests that earlier findings of no or weak smoking-AML associations may have been due to lack of subtype-specific analysis.