Six patients with hairy cell leukemia (HCL) were studied for surface immunoglobulin ( sIg ). In all five sIg -positive cases, the heavy chain isotype was IgG. We performed cytologic and cytochemical studies of sIgG + lymphocytes in normal peripheral blood and compared them with hairy cells. Normal sIgM + lymphocytes were also examined. sIgG + and sIgM + lymphocytes made up 0.9% and 6.1% of normal peripheral blood lymphocytes, respectively. Under a phase-contrast microscope, 76% of sIgG + lymphocytes showed cytoplasmic processes similar to those found on hairy cells, whereas most sIgM + lymphocytes had smooth surfaces. Tartrate-resistant acid phosphatase (TRAP) staining revealed that TRAP- positive cells accounted for 65% of sIgG + lymphocytes and 19% of sIgM + lymphocytes. Some (8.3%) of the sIgM + lymphocytes expressed sIgG concomitantly. When sIgM +, sIgM +, sIgG + lymphocytes were excluded, the percentages of cells with surface processes and of TRAP-positive cells in the remaining sIgM +, sIgG - lymphocytes were 10% and 12%, respectively. A very small proportion (0.2%) of sIgM -, sIgG - lymphocytes had cytoplasmic processes. These results indicate that normal sIgG + lymphocytes are cytologically and cytochemically different from most sIgM + lymphocytes and that the phase-contrast microscopic appearances and TRAP activity of sIgG + lymphocytes are similar to those of HCL tumor cells.