The population pharmacokinetics of theophylline was evaluated using 374 theophylline serum concentration measurements from 72 hospitalized patients through NONMEM analysis. An one-compartment open pharmacokinetic model with first-order absorption and first-order elimination was used. The effects of a variety of factors on Cl and Vd were investigated. Hypothesis testing to evaluated potentially significant factors produced a final regression model. There were about 1.25% per year decrease in Cl at the age of 18-77. Cl was reduced by 26.8% for patients with long history of theophylline administration and multiple dosings, and reduced by 33.9% in OLD patients. Sex, body weight, and coadministration of acetylspiramycin had no significant effects on Cl. Vd was proportional to body weight. The final regression model allowed a priori estimate of the theophylline pharmacokinetic parameters in the patients. These results may be helpful to a rational individualized theophylline dosage regimen.