The purpose of this study was to evaluate the frequency and clinical significance of diffuse hepatic uptake on 131I whole-body scan in 399 patients (53 males, 348 females) with well-differentiated adenocarcinomas of the thyroid. METHODS Two hundred and ninety-one diagnostic scans were performed 2 days after the administration of 74-370 MBq (2-10 mCI) 131I, and 824 post-therapy scans were done 3-5 days after the administration of 1.11-7.4 GBq (30-200 mCI) 131I. There was no evidence of liver metastasis in these patients. Liver and thyroid visualization on each 131I scan were graded from 0-4. To evaluate the incorporation of radioiodine to thyroglobulin and thyroid hormones, a patient's serum was extracted by 80% ethanol/20% trichloroacetic acid solution and analyzed by silica gel thin-layer chromatography. RESULTS Diffuse hepatic uptake (> Grade 2) was definitely seen in 239 of 399 (59.9%) of the patients and 397 of 1115 (35.6%) of the studies. In the diagnostic scans, 36 (12.0%) showed uptake in the liver. In post-therapy scans, however, the incidence of liver uptake increased according to increased doses of 131I (39.1% with 1.11 GBq, 61.5% with 2.775-3.7 GBq and 71.3% with 5.55-7.4 GBq). The more that uptake appeared in the residual thyroid, the more it appeared in the liver. There were 13 patients whose scans showed metastatic and liver uptake without any thyroid uptake. Fifteen patients showed diffuse liver uptake without uptake by the thyroid or metastasis. Follow-up studies of seven of these patients revealed metastatic lesions. Liver uptake on scan related to the fraction of 131I-labeled thyroglobulin in the serum. CONCLUSIONS Diffuse liver uptake indicated functioning thyroid remnant or metastasis. In a few cases, liver uptake without uptake by the thyroid or metastasis on whole-body scans suggests hidden metastases.