Attempts were made to develop a reliable test for the presence or absence of carcinogens in the environment. Certain plant materials suspected of affecting the development of esophageal cancer in man were applied to hamsters' upper gastrointestinal tract, including cheek pouch, in several long-term experiments. The materials tested, often with calcium hydroxide added, were 9 plants from Curaçao used in native teas and remedies, a tobacco (in snuff), and an alkaloid (arecoline) present in betel quid. Lesions developing after treatment with the plants Annona muricata, He/iotropium ternatum, Krameria ixina , and Acacia villose , and with arecoline, were a superficial spreading carcinoma of pouch epithelium, papillomas of esophagus (4), and advanced atypias (1 in pouch, 3 in esophagus). These lesions developed in relation to the cheek pouch route of application only, while none resulted after ingestion of a concentrated tea ( Acacia villosa ), or when administered in the diet ( Annona muricata , arecoline). The histologic types and distribution of the lesions in cheek pouch and esophagus suggested that they were caused by substances in the test materials tentatively presumed to be weaker or slower in action than the known chemical carcinogens.