The nucleoside analog 2-chlorodeoxyadenosine (2-CdA) has recently emerged as a most promising treatment for hair-cell leukemia (HCL). The response rates are high regardless of prior therapy, and the duration of complete responses (CR) after a single course of treatment is longer than with any other therapeutic agent. We investigated the presence of minimal residual disease (MRD) in ten HCL patients treated in our institution with 2-CdA. The presence of residual leukemic cells was investigated in patients in CR following one course of treatment, using the polymerase chain reaction (PCR) and heavy-chain immunoglobulin genes (IgH), or TCR delta derived clonospecific probes. Eight patients achieved a complete remission after a single course of treatment, as evaluated at 6 months. Among these patients, seven are still in CR with a median follow-up of 12 months (range, 6-20 months) and one has relapsed after 15 months. Using PCR, all the evaluable patients remaining in CR showed persistent evidence of detectable MRD with no sign of decrease over the observation period. From this small series, we conclude that a single course of 2-CdA does not eradicate HCL and that persistence of residual leukemic cells appears to be common in patients in complete morphologic remission. Whether persistence of MRD will have an impact on long-term outcome, or whether HCL patients in morphologic CR with persistent MRD will remain so, is a matter of longer follow-up.