The metabolism of human immunoglobulin D (IgD) was studied in 28 patients with various immunoglobulin disorders. IgD, the least abundant immunoglobulin, has a median serum concentration of 30 µg/ml, about 1/4 of the serum IgG concentration. The study used radioiodinated IgD to investigate its metabolic behavior. The results showed that the synthetic rate is the major factor controlling serum IgD concentration, and IgD is metabolized independently of other immunoglobulins. IgD was isolated from two sources: a patient with abundant IgD and a patient with D myeloma. The labeled IgD was used in 34 studies, with six patients receiving both preparations. The serum IgD level was directly related to the rate of synthesis, with differences as great as 50-fold among 27 subjects without IgD-synthesizing cell neoplasms. The median rate of IgD synthesis was 0.4 mg per kg per day, about 1-2% of the synthetic rates for IgG and IgA. The median serum level of IgD (0.023 mg per ml) was only about 0.2% of the median IgG level. The difference between relative serum levels (1:465) and synthetic rates (1:100) for IgD:IgG reflects the more rapid rate of IgD catabolism. The biological half-life of IgD was shorter than that of other immunoglobulins, with a median half-life of 2.8 days. The fractional catabolic rates of IgD and IgA were similar, while other immunoglobulins were catabolized at slower rates. Studies in three patients with disordered metabolism of IgA or IgG revealed normal IgD metabolism, indicating that IgD is metabolized independently from IgA or IgG. The fractional catabolic rate of IgD appears to be altered by the serum IgD concentration. Those subjects with high serum IgD levels tend to have relatively low fractional catabolic rates. This concentration-catabolism relationship for IgD is the opposite of that noted for IgG, where high serum levels are associated with relatively rapid IgG catabolism. IgD is largely (73%) in the intravascular compartment, contrasting with other 7 S immunoglobulins, for which only 40 to 50% of the total body IgG and IgA is in the intravascular compartment. The study highlights the unique metabolic characteristics of IgD, including its lower synthetic rate, shorter half-life, and distinct intravascular-extravascular distribution compared to other immunoglobulins. The findings suggest that IgD metabolism is independent of other immunoglobulin classes and is primarily controlled by synthetic rate.The metabolism of human immunoglobulin D (IgD) was studied in 28 patients with various immunoglobulin disorders. IgD, the least abundant immunoglobulin, has a median serum concentration of 30 µg/ml, about 1/4 of the serum IgG concentration. The study used radioiodinated IgD to investigate its metabolic behavior. The results showed that the synthetic rate is the major factor controlling serum IgD concentration, and IgD is metabolized independently of other immunoglobulins. IgD was isolated from two sources: a patient with abundant IgD and a patient with D myeloma. The labeled IgD was used in 34 studies, with six patients receiving both preparations. The serum IgD level was directly related to the rate of synthesis, with differences as great as 50-fold among 27 subjects without IgD-synthesizing cell neoplasms. The median rate of IgD synthesis was 0.4 mg per kg per day, about 1-2% of the synthetic rates for IgG and IgA. The median serum level of IgD (0.023 mg per ml) was only about 0.2% of the median IgG level. The difference between relative serum levels (1:465) and synthetic rates (1:100) for IgD:IgG reflects the more rapid rate of IgD catabolism. The biological half-life of IgD was shorter than that of other immunoglobulins, with a median half-life of 2.8 days. The fractional catabolic rates of IgD and IgA were similar, while other immunoglobulins were catabolized at slower rates. Studies in three patients with disordered metabolism of IgA or IgG revealed normal IgD metabolism, indicating that IgD is metabolized independently from IgA or IgG. The fractional catabolic rate of IgD appears to be altered by the serum IgD concentration. Those subjects with high serum IgD levels tend to have relatively low fractional catabolic rates. This concentration-catabolism relationship for IgD is the opposite of that noted for IgG, where high serum levels are associated with relatively rapid IgG catabolism. IgD is largely (73%) in the intravascular compartment, contrasting with other 7 S immunoglobulins, for which only 40 to 50% of the total body IgG and IgA is in the intravascular compartment. The study highlights the unique metabolic characteristics of IgD, including its lower synthetic rate, shorter half-life, and distinct intravascular-extravascular distribution compared to other immunoglobulins. The findings suggest that IgD metabolism is independent of other immunoglobulin classes and is primarily controlled by synthetic rate.