We evaluated the effect of beta blockers on thallium-201 (Tl-201) single photon emission computed tomographic (SPECT) imaging in 12 patients with coronary disease using an automated computer algorithm. Maximal exercise heart rate and blood pressure were reduced and exercise time was increased with beta blockers. Estimated stress defect size decreased from 47 +/- 36.3 gm during placebo treatment to 32 +/- 27.1 gm during beta blocker therapy (-32%; p less than 0.01). The placebo treatment redistribution defect was estimated to be 28 +/- 29.8 gm. It fell to 15 +/- 23.3 gm with beta blockade (-46%; p less than 0.005). All patients had a stress Tl-201 defect during placebo treatment and eight had redistribution defects consistent with residual scar. During beta blocker therapy, 2 of 12 patients had normal stress-redistribution studies and only five patients had redistribution defects. Beta blockade can reduce exercise and redistribution Tl-201 SPECT defect size significantly while simultaneously increasing exercise time and reducing angina. Beta blockers may unmask or may eliminate evidence of redistribution. Tl-201 SPECT imaging may be useful in defining the reduction in ischemia produced by cardiac drugs.