The cis- and trans-isomers of N-nitroso-3,5-dimethylpiperidine were administered separately in drinking water solution to groups of 20 female F344 rats for 50 weeks. The concentrations of the solutions were 0.72 m M for the cis-isomer and 0.14 mM for the trans-isomer. In both groups the animals died with tumors of the upper gastrointestinal (GI) tract, mainly carcinomas of the esophagus, at about the same time. A third group of animals was given a mixture of the two isomers in the ratio of 5 cis:1 trans, and these animals died more rapidly with the same upper GI tumors. The trans-isomer appeared to be a more potent carcinogen than the cis-isomer. The 3,5-dimethyl derivative is a less potent carcinogen than nitrosopiperidine.