Monoclonal antibodies (MAb) that detect specific lymphocyte subsets of man were tested for their reactivity with peripheral blood lymphocytes (PBL) and established cell lines of owl monkeys (Aotus trivirgatus) and marmosets (Saguinus spp). Results of these studies showed that certain determinants were conserved and that the pattern of reactivity observed in one genus (or even species) could not be used to predict the reactivity in another. On owl monkey PBL, reactivity equivalent to that on human PBL was observed with OKT11a, anti-Leu 3a, B1, and anti-HLA-DR MAb thus detecting T cell, helper/inducer T cell, B cell, and HLA-DR determinants. After neuraminidase treatment of owl monkey PBL, reactivity with anti-Leu 5 and OKT8 (T cell and suppressor/cytotoxic T cell determinants) was observed. Cell separation experiments indicated these determinants were found on lymphocytes with the same general properties as those of human origin. The use of these MAb to examine owl monkeys infected with Herpesvirus saimiri and tumor cell lines established from H. saimiri-inoculated monkeys revealed that the virus was found in OKT11a-positive, B1-negative cells. In chronically infected nondiseased animals, H. saimiri was found in anti-HLA-DR-negative cells and was restricted to anti-Leu 3a-positive cells (two animals) or was nearly equally distributed in anti-Leu 3a-positive and negative cells (one animal). Established H. saimiri tumor cell lines had the phenotype OKT11 a-positive, anti-HLA-DR-positive, B1-negative and were either anti-Leu 3a-positive or negative. Studies of interleukin 2-responsive tumor cells in short-term culture suggested the tumor was composed of virus-positive anti-Leu 3a-positive and negative populations.