Earlier studies of serum immunoglobulin D concentrations were hampered by the insensitivity of single radial diffusion, since most normal individuals have IgD concentrations in a range below or near the limit of sensitivity of that method. Using a sensitive double-antibody radioimmunoassay, we measured serum IgD in normal individuals from 28 weeks' gestational age to 70 years of age and in several groups of diseased individuals, many of whom had elevated serum IgE concentrations. The group mean serum IgD concentration in children one to 20 years of age was 13.65 IU/ml. Premature and term neonates had levels that did not differ significantly from each other (0.22 and 0.14 IU/ml, respectively), but that were far lower than serum IgD concentrations in normal children one to 20 years of age (P = less than 10-9), indicating that mature levels of IgD are achieved sometime during the first year of life. Normal adults aged 21 to 70 years, atopic children with or without eczema, children with serum IgE values greater than 2,000 IU/ml, and children with cystic fibrosis all had group mean IgD concentrations that did not differ significantly from that of normal children. In contrast, 20 patients with the hyper IgE syndrome had a mean serum IgD concentration of 94.22 IU/ml, significantly higher than the normal or any other group mean (P = less than 10-5).