To assess the predictive power of immunological and virological markers for the development of neurological syndromes, 39 HIV-1-infected infants with a mean age of 4.05+/-0.5 months and without neurological manifestations at enrolment were studied. They had neither been previously treated with antiretroviral therapy, nor had their mothers been given such treatment during pregnancy. They were routinely assessed for signs of neurological impairment during follow-up (19.54+/-3.37 months). Cox regression analysis was used to evaluate the risk of appearance of neurological signs, associated to viral load and T-lymphocyte subsets. A HR > 1 for viral load, and <1 for CD8+, but not for CD4+T-lymphocyte percentage, was observed, indicating that higher viral load and lower CD8+ T-lymphocytes percentages are risk factors for developing neurological signs. By applying the Kaplan-Meier method we found that infants with viral load > 5 1og10 copies/ ml or <20% CD8+T lymphocyte had higher relative risk for developing neurological impairment than those with these two parameters below or above these values, respectively. Finally, CD8+ T lymphocyte had a stronger prognostic value to predict neurological manifestations than viral load. Our data strongly suggest that in the early postnatal period viral load and CD8+ percentages are useful markers in predicting neurological impairment. To our knowledge, this is the first time that CD8+ T-lymphocyte levels are related to development of neurological disorders in AIDS.