Increasing numbers of children affected by HIV are being recognised in northern India. The present study aimed to evaluate the clinical profile of 516 children affected by HIV at the Pediatric Allergy and Immunology Unit, Advanced Pediatric Center, Postgraduate Institute of Medical Education and Research, Chandigarh, India, during the period January 1994 to May 2008. In total, 454 children (327 boys and 127 girls) infected by HIV were analysed. The median age at presentation was 54 months. Of these children, 401 (88.3%) acquired the infection vertically and 26 (5.7%) acquired it through transfusion of blood/blood products. Moreover, 156 children (34.4%) were asymptomatic at presentation to hospital. Common clinical features included fever (36.6%), respiratory infections (31.7%), lymphadenopathy (30.0%), hepatosplenomegaly (21.8%) and diarrhoea (18.1%); 299 children (65.9%) were malnourished. Triple drug antiretroviral therapy was initiated in 205 children. Children receiving such therapy showed significant improvement in clinical and immunological parameters. Furthermore, follow-up rates improved markedly following free supply of the drug. Therapy was very well tolerated. To conclude, physicians looking after children need to be familiar with the varying clinical presentation of HIV infection. To the best of our knowledge, this is the largest paediatric series on HIV infection from a single centre from any developing country.