The Koup et al. and Chiou et al. clearance estimation methods were evaluated in 19 chronic obstructive pulmonary disease (COPD)/asthmatic patients who were receiving aminophylline by continuous infusion. Estimated theophylline clearance (Clest) was determined using two serum concentrations obtained during the first few hours of therapy (1–16 hr) prior to achievement of steady state. Actual theophylline clearance (Clact) was determined after steady state conditions had been achieved (defined as 4–5 half-lives at the same infusion rate). The correlation between ClactandClestwas highly significant for both the Koup et al. and Chiou et al. methods, r = 0.865, p < 0.001, and r = 0.858, p < 0.001, respectively. The clearance estimation methods were compared with the Food and Drug Administration (FDA) dosage guidelines and shown to be clearly superior in predicting therapeutic steady state theophylline concentrations.