BACKGROUND A peripheral blood absolute lymphocyte count (ALC) of greater than 5 x 10(9)/l is considered the required minimum for diagnosis of chronic lymphocytic leukemia (CLL). Cases with low ALC (CLL-LLC), less than 5 x 10(9)/l, have not been included in the current staging systems, and would not be suspected of having CLL, or investigated for the disease, especially in the absence of clinical manifestations. On the other hand, the diagnostic value of the differential lymphocyte counts have not been emphasized. METHODS Cell suspensions from peripheral blood of previously untreated cases of CLL-LLC (n = 12) and typical CLL (n = 189) were analyzed for immunologic evaluation of surface immunoglobulin (SIg), mouse erythrocyte rosettes, CD5, CD19, CD20, CD22, and CD2, as well as cytochemical evaluation of tartrate-resistant acid phosphatase (TRAP). The results in CLL-LLC were compared statistically with typical CLL. RESULTS The ages of the 12 patients with CLL-LLC ranged from 47 to 84 years. The absolute lymphocyte counts ranged from 1.5 x 10(9)/l to 4.9 x 10(9)/l, and the percentage of lymphocytes in the differential leukocyte counts ranged from 52% to 93%. None of the patients had signs and symptoms of CLL or other conditions that may cause reactive lymphocytosis. CLL-LLC demonstrated similar characteristics to typical CLL, i.e., weak expression of monoclonal SIg, mouse rosette formation, positive CD5, high CD19 and CD20, negative CD22 and TRAP. No statistical differences existed between the immunologic markers or between SIg isotype distribution in the two groups. CONCLUSIONS Cases of CLL-LLC constituted 6% of B-CLL and would have been missed if immunologic investigation was not carried out because of the absence of absolute lymphocytosis and clinical manifestations of CLL. Persistent relative lymphocytosis of > or = 50% of the differential leukocyte count in older individuals (older than 50 years of age), is an indication for further investigation of CLL by immunophenotyping of peripheral blood lymphocytes and examination of bone marrow.