Paraffin-embedded sections of 77 peripheral T-cell lymphomas (PTCLs) were stained with several monoclonal antibodies, including the preferential T-cell markers Leu-22 (L60[CD43]) and UCHL1 (CD45RO). The staining characteristics of L60 and UCHL1 were compared to determine the value of each in the immunophenotypic analysis of PTCLs. Lineage specificity was evaluated among 39 B-cell lymphomas and 33 cases of Hodgkin's disease (HD). L60 and/or UCHL1 stained 95% of PTCLs, whereas L60 and UCHL1 alone stained 90% and 69% of cases, respectively. L60 demonstrated significantly greater numbers of immunopositive tumor cells than UCHL1 in 37% of the PTCL cases, principally because of enhanced marking of large, neoplastic cells. UCHL1 was a better marker in only 10% of the PTCL cases. L60 stained 33% of B-cell lymphomas, usually small lymphocytic or lymphoplasmacytic types. UCHL1 stained only 8% of B-cell lymphomas, all large-cell types. L60 and UCHL1 stained Reed-Sternberg cells and variants in three cases of nodular sclerosing HD. These results suggest that both L60 and UCHL1 are useful markers of PTCLs in routinely processed tissue. L60 is a more sensitive marker of large neoplastic T-cells than UCHL1 but is less lineage-specific. These antibodies are most effective when used as part of a panel of monoclonal antibodies.