We report a simple and robust method for sensitive quantitation of leukaemic cells in acute lymphocytic leukaemia. Chain determining region 3 (CDR3) of the immunoglobulin heavy chain gene is a precise genetic marker for a patient's leukaemic clone. Quantitation of the leukaemic lymphocytes was achieved by use of the polymerase chain reaction to detect CDR3 at limiting dilution of DNA samples. Five patients were studied and high levels (1 in 1 to 1 in 10) of leukaemic cells were detected at diagnosis or relapse. Leukaemic cells were detected in remission marrows from three patients, at levels of 1 in 1000 to 1 in 100,000. All five patients showed a 1000 to 100,000-fold reduction in the levels of leukaemic cells after induction therapy. This technique should prove useful for monitoring therapy and may help predict outcome.