Ribonucleotide reductase (RNR) is a cytoplasmic enzyme that is essential for DNA synthesis. Its activity is strongly associated with cell proliferation. We assessed the value of immunostaining for RNR in distinguishing between reactive mesothelia (RM), malignant mesotheliomas (MM) and adenocarcinomas (AC) in serous effusions.Cytocentrifuged cell smears of serous effusions from 38 RM, 10 MM and 36 AC were immunostained with the monoclonal antibody KM1054 raised against the R2 subunit of RNR (RNR-R2) using the labeled streptavidin-biotin method. Quantitative RNR-R2 values were determined by counting the percentages of immunoreactive cells.RNR-R2 immunostaining was confined to the cytoplasm. The median RNR-R2 value was 1.4% (range, 0-7.9%) for RM, 11.2% (4.1-15.3%) for MM and 12.1% (2.0-40.6%) for AC. Significant differences in RNR-R2 values were found for both AC versus RM (P or = 7% was found in 30 of 36 AC, 8 of 10 MM and 2 of 38 RM.RNR-R2 immunostaining can be useful as an adjunct for differentiating AC or MM from RM in serous effusions.