Theobromine and theophylline have a limited therapeutic use and in addition they occur in plants used in the preparation of a number of widely consumed drinks. Thus most of the population must be exposed to both compounds. Chromosome abnormalities are caused by both theobromine and theophylline in plant cells and in mammalian cells in culture, and both have anti-mitotic activity. While they are fairly potent mutagens in Escherichia coli and other lower organisms the rather scanty available evidence suggests that they are not mutagenic in mammals. The difference in mutagenic activity may be due to the reported inability of E. coli to demethylate these compounds, a process which occurs readily in mammals including man. The structure-activity relationships of these compounds are complex but the available evidence suggests that methylation at position 1 is the most important for both mutagenic activity and the anti-mitotic effect while methylation at position 3 is of most importance in the action on chromosomes.