Cytokeratins are intermediate filaments found within basal and secretory epithelial cells. Antisera raised against cytokeratins are available but frequently differ in specificity. Many are incompletely characterized for their reactivity against epithelial components. Cytokeratin (Cyto) P is a polyclonal antisera specific for 56 and 64 kd cytokeratins. Cyto M is a pool of monoclonals reacting against 40, 46, 50, 52, 58, and 65-67 kd cytokeratins. Initially, utilizing immunohistologic techniques, we evaluated these two antisera for their ability to distinguish between prostatic tissues of benign (benign prostatic hypertrophy [BPH]) or malignant (carcinoma of the prostate [CAP]) origin in the 34 cases evaluated. Specimens were analyzed for both Cyto P and Cyto M reactivity, as well as for the degree of reactivity. Lastly, in an effort to determine the morphologic relationship of atypical hyperplasia (AH) with either BPH or CAP, nine additional prostate specimens were analyzed. Cyto P was reactive in 8 of 8 (100%) BPH specimens and in 2 of 26 (8%) CAP specimens. Mean Cyto P degree of reactivity in the positive specimens was greater in BPH than in CAP (2.6 vs. 1.0). Cyto M reactivity was present in 8 of 8 (100%) BPH specimens and in 23 of 25 (92%) CAP specimens. Mean Cyto M degree of reactivity in the positive specimens was greater in CAP than in BPH (3.6 vs. 2.8). Cyto P was reactive in 3 of 9 (33%) AH specimens, with a mean degree of reactivity of 2.7. Cyto M was reactive in 9 of 9 (100%) AH specimens, with a mean degree of reactivity of 3.9. Cyto P reacted with only the basal cells, whereas Cyto M reacted with basal as well as secretory cells. These differences appeared to be the result of the differential reactivity of basal cells, which are present in BPH but absent in CAP. In summary, Cyto P and Cyto M are potentially useful markers in differentiating BPH from CAP, and it appears that AH is immunohistopathologically related to both.