Objective-To investigate the immunogenicity of Haemophilus influenzae type b (Bib) conjugate vaccines in children with sickle cell disease. Design-Open study. Setting-Haemoglobinopathy clinic. Subjects-Children with homozygous haemoglobin SS disease (HbSS), sickle haemoglobin C disease (HbSC), and sickle-beta circle thalassaemia disease (HbS-beta Thal) . Interventions-Children over the age of 2 years received a single dose of Hib-tetanus toroid conjugate vaccine (PRP-T). Main outcome measures-Antibody response to Bib polysaccharide (PRP) approximately one month after vaccination. Results-77 children over the age of 2 years were studied, 55 with HbSS, 16 with HbSC, and six with HbS-beta Thal. Before vaccination, 44% had anti-PRP IgG titres less than the level associated with long term protection (1.0 mu g/ml). After a single dose of PRP-T all children mounted an antibody titre >1 mu g/ml. Geometric mean anti-PRP IgG titre achieved postvaccination (45.2 mu g/ml 95% confidence interval (CI) 31.6 to 64.8) was comparable to that of a healthy population. Children with HbSC, however, had a significantly higher antibody titre postvaccination (91.1 mu g/ml; 95% CI 32.7 to 254.4) than the children with HbSS (36.7 mu g/ml; 95% CI 25.1 to 52.9). Conclusions-Children with a diagnosis of sickle cell disease who are over the age of 2 years make a vigorous antibody response to a single dose of PRP-T vaccine and hence we suggest unimmunised individuals in this group should receive a single dose of a Bib conjugate vaccine.