Twenty-two IgG-positive human lymphoblastoid cell lines and normal peripheral blood lymphocytes were studied for surface and cytoplasmic IgG, IgG subclasses, IgD and IgM, using monospecific fluorescein- and rhodamine-conjugated F(ab')2 antibody fragments, and for secretion by double antibody radioimmunoassay. Several parallel observations and several differences in IgG subclass expression were noted between cell lines and normal lymphocytes. Surface IgG2 was frequently expressed in normal IgG-positive lymphocytes but was seldom expressed in cell lines. Cell lines resembled normal IgG-positive lymphocytes in the frequent expression of cytoplasmic IgG3 and IgG4, often without secretion. Cell lines and normal lymphocytes both showed more frequent distribution of IgG and IgG subclasses in cytoplasm than in surface immunoglobulin, and often a discrepancy of surface versus cytoplasmic IgG subclass. A good correlation was noted between surface, cytoplasmic and secreted IgG1. Despite a predominance of IgG2 and IgG4 surface IgG subclasses, and IgG3 and IgG1 in cytoplasm, secreted immunoglobulins from normal lymphocytes in short-term culture showed a similar distribution of IgG subclasses to that seen in normal sera. Multiple expression of IgG subclasses was much more frequent in IgG-positive cell lines than in normal peripheral blood lymphocytes, both in surface and cytoplasmic IgG.