Seventy-six patients with thyroid nodules were studied. Initially, 74 MBq of thallium-201 was injected. The thyroid gland was imaged 15 min (early) and 3 h (delayed) after the injection. Thereafter, 185 MBq technetium-99m pertechnetate was injected. Immediately after the injection, a 1-min perfusion image was acquired, followed by an image at 20 min. Increased early and delayed Tl-201 uptake compared with the contralateral thyroid tissue was adopted as the criterion for malignancy. Sensitivity, specificity and negative predictive values were found to be 85%, 64% and 78%, respectively, in operated patients, but these values were 86%, 87% and 95 %, respectively, in the whole group, including patients followed with fine-needle aspiration biopsy. With the purpose of investigating the relationship between perfusion and early Tl-201 uptake, both perfusion and early images were graded comparing nodular activity with contralateral thyroid activity. There was a poor correlation between perfusion and Tl-201 uptake. The correlation was even worse in hyperactive nodules. It is concluded that early and delayed Tl-201 imaging should not be used in the differential diagnosis of cold nodules and that early Tl-201 uptake seems to be more closely related to factors other than perfusion.