The present investigation has been undertaken to analyze absolute and relative CD5+ B-cell numbers in patients with lupus erythematosus (LE), and concomitant B-CLL, and to monitor them under therapy. Peripheral blood lymphocytes of LE-patients, and healthy controls were analyzed by flow cytometry and direct immunofluorescence technique. Patients were treated with low-dose methotrexate (MTX). Before and during MTX treatment laboratory monitoring has been done. LE-patients had increased percentages of CD5+CD19+ as compared to controls (p < 0.0002), the absolute number of CD5+ B-cells was equal in controls and patients. Autoantibodies were positively correlated to the number of CD5+ B-cells in LE-patients. In a total of 140 LE-patients one male patient suffered from both LE and B-CLL (0.7%). He had increased absolute and relative CD5+ B-cells. MTX induced significant decrease of both total B-cell numbers, and CD5+ B-cells. The decrease of CD5+CD19+ cells was more pronounced than the decrease of total B-cells. Apoptosis rate increased in parallel to the drop-down of elevated CD5+CD19+ cells. Peripheral T-cell subsets remained stable under low-dose MTX. Both absolute and relative numbers of CD5+CD19+ cells should be taken into account in patients with LE. MTX seems to decrease B-cells, and preferentially to down-regulate B-cells expressing the CD5 molecule, which opens new therapeutic options and cell biological activities. The mechanism is unclear but apoptosis induction seems to be likely.