BACKGROUND The clinical, neuroimaging, virologic and evolutive characteristics of progressive multifocal leukoencephalopathy (PML) in 35 AIDS patients are studied. METHODS PML was diagnosed by clinical and neuroimaging criteria in 32 patients and by autopsy in other three. The detection of JC virus (JCV) was done by PCR and further hybridization of the amplified DNA in peripheral blood lymphocytes, urine and CSF. RESULTS 127 of 930 HIV positive patients were admitted by neuropsychiatric symptoms and of them 35 (SD 27.6%) by PML. The PML patients had a mean CD4 lymphocytes count of 75.3 (82.0)/x 10(6)/l and a HIV viral load of 330,698 (538,971) copies of RNA/ml. Thirty patients did not receive any anti-retroviral therapy or only transcriptase inhibitors monotherapy and five triple anti-retroviral therapy, including a proteases inhibitor. Multiple hypodense lesions on CT (53.1%) and T2 hyperintense lesions on MRI (58.3%) were the most frequent neuroimaging findings. JCV was detected in 20/21 (95.2%) LMP patients: 18/19 detections in lymphocytes, 6/8 in CSF and 4/6 in urine. The mean survival without and with antiretroviral therapy were 3.0 (0.47) and 21.4 (4.4) months (p < 0.001) in 34 patients followed. PML progressed to death in 31/34 patients (91.2%), and remained stable in 3/34 (8.8%). A patient was lost for follow-up. CONCLUSIONS The application of clinical and neuroimaging criteria and the detection of JCV in CSF are useful for high presumption diagnosis of PML without brain biopsies. JCV detection in lymphocytes and in urine have a much lower predictive value. The evolution and survival of this disease can improve with triple anti-retroviral therapy including a protease inhibitor.