The clonal origin of an IgAκ B cell leukemia in a 71-yr-old man (WF) was examined using a monoclonal anti-Id antibody and a panel of monoclonal anti-V(H) antibodies. Immunofluorescent studies revealed that all surface IgA1≃+ leukemic cells in WF's blood and 10% of the IgM+ B cells in his bone marrow expressed the WF Id. Three percent of the IgA1κ+ leukemic cells in blood also expressed γ-chains in their cytoplasm. Approximately 0.1%, 1%, and 10% of bone marrow mononuclear cells, respectively, expressed μ-chains, γ-chains, and α-chains in their cytoplasm, but no detectable light chains or surface immunoglobulins. These μ-, γ-, and α-positive cells had the convoluted nucleus and narrow cytoplasm characteristic of normal μ+ pre-B cells. Sequential isotype switching among this unusual pre-B population was indicated by co-expression of μ-chains and α-chains by 11% and 63%, respectively, of the γ pre-B cells. These pre-B cells and the surface α-chains and cytolasmic γ-chains of the leukemic B cells were reactive with one of four monoclonal anti-V(H) antibodies. The data suggest malignant transformation of the clone before isotype switching, and also imply light chain precommitment at the pre-B cell level of differentiation.