A series of 359 male patients with 424 cancer lesions of the oral cavity and oropharynx identified at a US Department of Veterans Affairs Medical Center were divided according to site of origin of the lesion and compared with 2,280 controls from the same hospital with respect to exposure to tobacco smoking and alcohol drinking. Sites of origin were: floor of the mouth (153), oral tongue (50), anterior tonsillar pillar (49), soft palate (44), lingual aspect of retromolar trigone (11), alveolar ridge (5), buccal mucosa (4), and hard palate (2). Forty-one patients had cancers in multiple sites. Tobacco smoking was more strongly associated with soft-palate lesions than with lesions in more anterior sites. Patients with cancer of floor of the mouth and oral tongue had higher odds ratios for alcohol drinking than subjects with cancers of other sites. This study supports the hypothesis of the carcinogenic effect of tobacco smoke and alcoholic beverages on the oral mucosa through direct contact.