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To describe the natural history of advanced HIV disease in patients treated with zidovudine.Longitudinal, observational study.Twelve academic and community-based sites.Eight hundred and sixty-three patients with AIDS or AIDS-related complex (ARC) with a CD4+ lymphocyte count <250 × 106/1, who first received zidovudine between 15 April 1987 and 14 April 1988.Survival, progression to AIDS and first development of specific opportunistic illness.Median survival after initiation of zidovudine therapy ranged from >900 days in patients with a baseline CD4+ lymphocyte count ≥150 × 106/1 to 560 days in patients with a CD4+ lymphocyte count < 50 × 106/1. Other factors associated significantly with poorer survival were diagnosis of AIDS (versus ARC), baseline age ≥40 years, hematocrit < 35%, and diminished functional status. In patients with ARC at enrollment, median time of progression to AIDS ranged from 810 days in patients with a CD4+ lymphocyte count ≥150 × 106/1 to 310 days in patients with a CD4 + lymphocyte count < 50 × 106/1. Rates of development of specific opportunistic infections or neoplasms and HIV encephalopathy were determined for different baseline CD4 + lymphocyte count ranges. Myelosuppression was significantly more common in patients with CD4+ lymphocyte counts ≥100 × 106/1. Sixty-five per cent of patients with a CD4 + lymphocyte count ≥100 × 106/1 and 51% with a CD4+ lymphocyte count < 100 × 106/1 continued to receive zidovudine 2 years after starting therapy.We describe the natural history of a cohort of patients treated with zidovudine for advanced HIV disease. These CD4+ lymphocyte count-stratified estimates of disease progression should provide prognostic information useful in the clinical management of advanced disease and the design of future studies.