As several reinjection procedures have shown encouraging results in terms of imaging, we investigated whether the kinetics of thallium-201 would differ between the standard stress-redistribution-reinjection approach and the stress-immediate reinjection approach. In 53 consecutive patients with undiagnosed chest pain, 75 MBq (2 mCi) 201Tl was injected at maximal exercise. In 26 of these patients (group I), 37 MBq (1 mCi) 201Tl was reinjected immediately after completing the exercise images (the immediate reinjection procedure) and in 27 patients (group II), 37 MBq (1 mCi) 201Tl was reinjected after completing 3-h redistribution images (the standard reinjection procedure). Mean peak 201Tl blood activity after exercise was 17.7+/-12.5 kBq/ml (4.8+/-3.4 mCi/ml) for group I versus 16.4+/-9.2 kBq/ml (4.4+/-2.5 mCi/ml) for group II (NS). The relative increase in 201Tl blood activity after reinjection of half the initial dose [37 MBq (1 mCi)] exceeded 50% of the initial peak in both groups. The relative amount of 201Tl delivered to the myocardium was assessed by the area under the curve after both exercise and reinjection, and was 117%+/-72% for group I and 112%+/-73% for group II (NS). Blood clearance of 201Tl was at least biexponential. Mean early decay constants (lambda 1) after exercise and reinjection were 0.30+/-0.18 min-1 and 0.22+/-0.046 min-1 respectively for group I (T 1/2 2.3 min and 3.2 min respectively, NS), and 0.30+/-0.12 min-1 and 0.24+/-0.07 min-1 respectively for group II (T1/2 2.3 min and 2.9 min respectively, NS). For both procedures no significant differences were found between lambda 1 after exercise and lambda 1 after injection. The mean late clearance (lambda 2) from the blood was 0.032+/-0.056 min-1 and 0.012+/-0.012 min-1 respectively for group I (T1/2 21.6 min and 57.7 min respectively, NS), and 0.036+/-0.030 min-1 and 0.014+/-0.014 min-1 respectively for group II (T1/2 19.3 min and 49.5 min respectively, NS). Also, no significant differences were found between lambda 2 after exercise for both groups and between lambda 2 after reinjection for both groups. We conclude that reinjection of 37 MBq (1 mCi) 201Tl (half the initial dose) results in a relative increase in the initial peak and a relative increase in the amount of 201Tl delivered to the myocardium of more than 50% for both the standard and the immediate reinjection procedure. The clearance of 201Tl from the blood was not influenced by exercise or by the time of reinjection. Based on 201Tl kinetics as measured in the peripheral blood, there is no reason to postpone reinjection until 3-4 h following exercise.