• To better define the clinical and biological evolution of infants after vertical human immunodeficiency virus type 1 infection, we analyzed 94 consecutive infected patients followed up after their first clinical symptoms. The expression of clinical symptoms and biological abnormalities followed a bimodal distribution, some patients having an early and severe disease and the others having a slowly progressive one. One third of our patients suffered from early onset of opportunistic infection (OI). These patients had a significantly higher incidence of severe encephalopathy compared with patients without OI. The rate of survival at 3 years was 48% ± 24%. In contrast, the patients without early OI or severe encephalopathy had a probability of survival at 3 years of 97%±3%. This probability was not modified by the occurrence of bacterial infection or lymphoid interstitial pneumonitis. Lymphoid interstitial pneumonitis occurred at a mean age of 29 months, significantly later than OI or severe encephalopathy. Laboratory results at initial examination were correlated with clinical symptoms. Thus, when the number of CD4 lymphocytes was less than 500/mm3, children suffered more frequently from life-threatening symptoms (OI and severe encephalopathy): 15 of 22 vs 14 of 69. The same was true when the lymphocytes did not proliferate after antigenic stimulation, when anti-p18 and/or anti-p25 antibodies were absent in the serum, and when p24 antigen was detected in serum. Finally, severe encephalopathy was associated with low anti–human immunodeficiency virus cerebrospinal fluid antibody titer, whereas 88% of patients with moderate or no encephalopathy had signs of intrathecal anti–human immunodeficiency virus antibody synthesis. In conclusion, a subgroup of patients expressed very early signs of severe immunodeficiency and encephalopathy, whereas the majority of patients had a longer survival and less severe clinical symptoms during their first years of life than previously thought.