N' Nitrosonornicotine (NNN) and N' nitrosoanabasine (NAB) were synthesized and administered in drinking water to male Fischer rats for 30 weeks (total dose, 630 mg). 1,4 Dinitrosopiperazine (DNPI) served as the positive control. By 11 mth, all surviving rats given NNN developed esophageal tumors (12/20); 1 had a pharyngeal tumor and 3 had invasive carcinomas originating in the nasal cavity. During the same time, only 1 of 20 rats given NAB developed esophageal tumors. Compared to the strong esophageal carcinogen DNPI, NNN was a moderately active and NAB a weak carcinogen. NNN (0.3-90 parts per million) in chewing tobacco was related to the observation that cancer of the oral cavity and esophagus in man is correlated with the chewing of tobacco.