We report a case of persistent polyclonal lymphocytosis in an infant. The circulating lymphocytes were of a small to medium size and a small proportion were larger and had lymphoplasmacytoid features. The presence of either an infectious or mutagenic agent was excluded. The polyclonal B-cell nature of the lymphocyte was demonstrated by immunological markers and confirmed by Southern blot analysis and by polymerase chain reaction targeting immunoglobulin genes. In contrast to the common form of polyclonal lymphocytosis, this case was not associated with HLA-DR7 and/or abnormalities of chromosome 3, p53 or Bcl2/IgH. Whether this lymphocytosis represents a premalignant or a benign condition remains uncertain, although there has been no progression to date.