Metabolic interactions between theophylline and several other drugs have been described in a number of studies. They may be of importance because of the narrow therapeutic range of theophylline. A significant risk for interactions has been considered to exist only with drugs metabolized by oxidative enzyme systems, and thus is not expected to occur with isoniazid. However, an increased clearance of theophylline with oral isoniazid medication has been reported. On the other hand, we found a significant increase in plasma levels of intravenously infused theophylline, and a corresponding decrease in plasma clearance of theophylline, when isoniazid was administered orally, compared to similar infusions in these individuals without concomitant isoniazid medication. The effect was seen irrespective of acetylator status. In five of the seven subjects an increase of isoniazid half-life and AUC was seen with theophylline, but this increase was not statistically significant.