This study was designed to evaluate the effects of intravenous theophylline given before intravenous adenosine for thallium-201 imaging. Sixteen patients with known reversible thallium-201 defects were randomized to a double-blind crossover study of a 45-minute infusion of placebo or theophylline (given as the ethylenediamine salt, aminophylline, mean concentration 16.1 mg/L) before adenosine thallium-201 imaging. Adenosine was infused for 6 minutes at a rate of 140 micrograms/kg/min. Thallium-201 (2.5 to 3.0 mCi) was administered after 3 minutes of infusion. Blood pressure, heart rate, symptoms, and the electrocardiogram were monitored continuously. Planar thallium-201 imaging was obtained in three standard views and was interpreted using blinded segmental analysis and computerized quantitation. Systolic and diastolic blood pressure at baseline and during adenosine administration were similar following treatment with theophylline and placebo. The increase in heart rate observed during adenosine infusion was significantly reduced by theophylline pretreatment. Adenosine-induced symptoms (both cardiac and noncardiac) as well as ischemic electrocardiographic changes were significantly reduced after theophylline infusion (p < 0.05). In one patient, Mobitz type II heart block seen during adenosine infusion following placebo was absent with theophylline pretreatment. The size of adenosine-induced thallium-201 defects was unchanged by theophylline infusion using either segmental analysis (8 +/- 4 vs 9 +/- 5) or a computerized score (47 +/- 27 vs 45 +/- 21). Despite reduction in both symptoms and ischemic electrocardiographic changes, theophylline does not alter thallium-201 imaging following intravenous adenosine infusion.