This case-control study evaluates the relationship between leukemia and the work histories of active and retired employees of a large petroleum company. The study includes 69 cases with leukemia and 284 matched controls. Employment in production-related work in the oil and gas division was associated with myelogenous leukemia (odds ratio [OR] = 2.0, 95% confidence interval [CI] = .97 to 4.2) and particularly with acute myelogenous leukemia (OR = 2.8, 95% CI = 1.1 to 7.3). The association with acute myelogenous leukemia was strongest for subjects in the highest tertile (32+ years) of duration of employment in oil- and gas production-related work (OR = 8.7, 95% CI = 2.0 to 37), and there was a consistent trend of increasing ORs with increasing duration of employment (P = .01). No clear association was observed for refining division work and leukemia. This is the first epidemiologic study reporting a positive association between oil and gas field work and acute myelogenous leukemia.