Immunoglobulin-secreting cells (ISC) in the peripheral blood are active effectors of the human immune defence system on their way to their site of action. We combined immunomagnetic cell separation and ELISPOT to study the expression of maturation markers and homing receptors (HR) on these cells in healthy volunteers. The results revealed that although highly differentiated, peripheral blood ISC are remarkably heterogeneous both with respect to their expression of maturation markers and HR. Moreover, significant differences were demonstrated between the various isotypes. Fewer IgA-secreting cells expressed both markers of early maturation (HLA-DR, HLA-DQ, CD20, and CD21) and of more mature B cells or plasma cells (CD28, CD38, and alpha-syndecan) compared with IgG- and IgM-secreting cells. IgA-secreting cells also showed the lowest proportion of cells positive for the peripheral lymph node HR, L-selectin, or the skin HR, cutaneous lymphocyte antigen (CLA). By contrast, the expression of mucosal HR on IgA-secreting cells did not reveal a more pronounced homing attitude to mucosal tissues than IgG- or IgM-secreting cells. We conclude that peripheral blood ISC are a heterogeneous cell population and that IgA-secreting cells seem to differ from the other isotypes both in respect of expression of HR and the various maturational markers studied.