A group of 52 patients with malignant uveal melanoma treated by primary enucleation in 1977-1979 was studied to determine the frequency of immunoreactivity for cytokeratins (CK) in primary and metastatic melanoma, the CK types present, and the prognostic significance of CK expression. By immunohistochemistry, monoclonal antibody (MAb) V9 to vimentin reacted with all 52 formalin-fixed, paraffin-embedded primary tumors and all 31 metastases from 11 patients. MAb CAM 5.2 to CK 8 and 18 reacted with 20 and MAb CY-90 to CK 18 with 25 primary melanomas, whereas MAb KS-B17.2 and MAb CK5 to CK 18 labeled 8 and 6 tumors, respectively. Antibodies to CK 13 and CK 19 each labeled single cells in one specimen, and other CK types were not detected. In 6 primary melanomas, only a few tumor cells were immunopositive for CK 8 and 18, but in 17 cases up to one quarter, and in 2 tumors more than one quarter, of them were labeled. The positive cells were spindle, epithelioid, or intermediate in shape, and tended to be more frequent in mixed than in spindle cell melanomas. MAbs CAM 5.2 and CY-90 did not react with any of the 16 liver metastases, but labeled 7 of 15 other metastases. Metastases were somewhat more common when the primary tumor was immunoreactive for CK 8 and 18, apparently because CKs were more frequent in mixed cell melanomas. Although CK expression is of diagnostic significance and can denote low levels of epithelioid differentiation, it is not an independent prognostic factor in malignant uveal melanoma.