The indications and usefulness of outpatient serum theophylline determinations were prospectively evaluated by doing 151 of these studies in 137 consecutive cases of chronic obstructive pulmonary disease. We found that evaluations were done for the following three groups of indications: group A, worsening bronchospasm; group B, stable asymptomatic cases, and group C, symptoms suggesting theophylline toxicity. When the three clinical groups were compared for frequency of nontherapeutic values, only an increased frequency of subtherapeutic values in patients with bronchospasm (group A) was significant (P<.01). Increasing the dosage up to 15 mg per kg of body weight a day while theophylline determinations are pending appears to be safe in this group of patients. Toxic symptoms were rarely associated with concentrations greater than 20 mug per ml (3/13) and infrequently occurred in patients with concentrations greater than 20 mug per ml (3/29). Nontherapeutic theophylline values did not always result in an adjustment of theophylline dosage. This was influenced by a correlation of symptoms, timing of the theophylline determination and the use of other bronchodilators.