A 55-year-old man was initially given a diagnosis of chronic lymphocytic leukemia (CLL) in April 1994 at age 44 years. After a period of observation, he was treated for progressive disease with chlorambucil in 1996 and again in 2002. In 2003, a prognostic marker evaluation showed that his CLL cells displayed “high-risk” biologic factors (unmutated Ig heavy chain variable region, and expression of CD38 and ζ-chain-associated protein 70) for progressive disease.1 The patient then developed cytopenia and was treated for progressive CLL in October 2003 with one cycle of high-dose dexamethasone (200 mg m−2 day−1 × 5 days) and rituximab (375 mg m−2 week−1 × 4 weeks) (Rituxan; Biogen Idec, Inc. and Genentech, Inc.; South San Francisco, CA), with an improvement in his blood counts. In 2005, he was treated on a phase one clinical trial with a single subcutaneous dose of CpG 7909 (ProMune; Pfizer Inc; New York, NY) (a new class of investigational synthetic oligonucleotide agonists of Toll-like receptor 9). This resulted in a short-term decrease in his lymphocyte count. In June 2005, the patient was again treated for progressive CLL causing cytopenias with high-dose methylprednisolone (1,000 mg m−2 day−1 × 5 days) and rituximab (375 mg m−2 week−1 × 4 weeks). He had a good response and was in remission until April 2006, when he developed drenching night sweats, fever, dry cough, back pain, and weight loss. Physical examination and chest radiographs were unremarkable. CT scan of the chest showed moderate bilateral axillary lymphadenopathy, mild bilateral hilar, and mediastinal lymphadenopathy, along with diffuse, finely nodular opacities in both lungs (Fig 1).