MIB-1 is useful in evaluating proliferative activity and in predicting the aggressiveness in a variety of tumors. To investigate if MIB-1 immunoreactivity can add prognostic information to conventional prognostic variables in papillary thyroid carcinoma (PTC), 30 PTCs were evaluated using the MIB-1 antibody. For comparison, 10 follicular thyroid carcinomas (FTC), 8 anaplastic thyroid carcinomas (ATC), and 96 follicular thyroid adenomas (FTA) were similarly analyzed. The median MIB-1 index was 0.5% in FTA, 1.9% in PTC, 2.7% in FTC, and 16.2% in ATC. The 13 tumors from patients classified as having aggressive PTC (defined as dead from disease, persisting disease, or the occurrence of distant metastases) had significantly higher MIB-1 index (median, 5.4%) than the 17 patients with nonaggressive disease (median, 1.1%). MIB-1 index 1.85% or more was found to be an independently significant risk factor for a less favorable clinical course in PTC. Because of overlap of single values the utility of MIB-1 index as a clinical test is somewhat limited. Still, at levels where no overlap occurs (MIB-1 index 2 3.2% or ' 0.5%) the index seems to add information to the established prognostic parameters. MIB-1 index should therefore be considered in routine histopathology of PTC.