Cytogenetic studies of bone marrow were performed in 230 consecutive cases of patients with chronic granulocytic leukemia (CGL) admitted to the National Cancer Institute since 1961. Twenty patients lacked the Philadelphia (Ph1) chromosome. All were previously untreated. When compared with Ph1-positive patients, CGL patients with Ph1-negative disease had a higher median age (60 compared with 42 years) and were diagnosed at lower median leukocyte (75,000) and platelet counts (170,000). Their response to chemotherapy was generally poor, with a median survival of 15 months compared with 44 months for the Ph1-positive group. Four patients survived more than 5 years and two, more than 10 years. Thirty-five per cent of the Ph1-negative patients had aneuploid cell lines of various percentages. Absence of the Ph1 chromosome in patients with the hematologic characteristics of CGL is a bad prognostic sign.