Ganglioside expression on adult T-cell leukemia (ATL) and human T-cell lymphotropic virus type I (HTLV-I)-infected cells was determined by using a panel of monoclonal antibodies. ATL lines and HTLV-I-infected cells specifically expressed GD2. Leukemia cells from ATL patients generally expressed low levels of GD2 but the percentage of GD2+ cells increased up to 40-70% after in vitro culture in the presence of interleukin 2 for about a week. No other type of leukemia cells and normal peripheral T cells expressed GD2 during in vitro culture under the same conditions. The appearance of GD2 in the cultured ATL cells corresponded with the expression of p40tax, a product of the HTLV-I gene. Peripheral lymphocytes infected with a p40tax-expressing retroviral vector expressed high levels of GD2 in comparison with control lymphocytes containing the neomycin-resistance gene alone. The apparently increased levels of beta-1,4-N-acetylgalactosaminyltransferase (GM2/GD2 synthase) mRNA in these cells were demonstrated by reverse transcription-polymerase chain reaction analysis. Concordance between mRNA expression for the HTLV-I tax1/rex1 genes and the beta-1,4-N-acetylgalactosaminyltransferase gene was also observed in uncultured ATL cells. These results suggest that high GD2 expression was due to neosynthesis from precursor GD3 by increased expression of this enzyme induced by p40tax in vitro and in vivo.