Herpes simplex virus-infected cells induce high interferon-alpha (IFN-alpha) production in infrequent cells among peripheral blood mononuclear cells (PBMC), designated natural IFN-alpha producing (NIP) cells. The properties of such NIP cells were compared with defined populations of leucocytes by means of flow cytometric analysis and sorting. The NIP cells are characterized as a discrete population of cells with high forward and low to intermediate orthogonal light scattering, similar to that of early progenitors of myeloid and lymphoid cells. However, they appear to lack the stem cell-associated molecule CD34. Furthermore, NIP cells cannot be localized to the myeloid line of cell differentiation, because they do not express the CD33, CD13, CD11b, CD15 or CD14 antigens. Neither do they express CD10 and CD19 antigens which are present in all stages of B-cell differentiation plasma cells excepted, nor CD7 antigens expressed on early T cells. In combination with previous results, our data support the view that the NIP cell is a unique and distinct cell type in peripheral blood, possibly with a physiological role in the defence against certain viral infections.