Whole body metabolic rate is elevated after administration of methylxanthines, but the mechanism by which this occurs is not clear. We have investigated the hypothesis that this increase in metabolic rate is in part due to increased physical activity. Metabolic rate and spontaneous cage activity of Fischer 344 rats were measured over a 24-h period before and during aminophylline treatment. Weight, food, and water consumption were also measured. Our results show an increase in metabolic rate with a simultaneous increase in spontaneous activity over the 24-h period. These results are consistent with the hypothesis that increased physical activity is in part responsible for the increase in cellular metabolism that follows administration of aminophylline.