Hyperimmunoglobulinemia, and other manifestations of B-cell stimulation, have been reported frequently in adults with type 1 Gaucher disease. We investigated the occurrence of hyperimmunoglobulinemia in 23 pediatric patients with type 1 Gaucher disease and studied the effects of early initiation of alglucerase/imiglucerase therapy on these abnormalities. We found that the incidences of increased levels of IgG, IgA, and IgM at pediatric age, as observed in our patients, were 3.2-fold, 4.3-fold and 5.1-fold higher, respectively, than the incidence in adult patients, and correspond with disease severity. Seventy-one percent of our pediatric patients had elevation of more than 1 immunoglobulin isotype, and 38% had elevations in all 3 isotypes. With sustained enzyme replacement therapy, substantial improvement, or normalization of IgA and IgM levels were obtained in most patients, while decline in IgG levels was less likely to occur. The presence of hyperimmunoglobulinemia in the majority of our pediatric patients suggests that early-onset production of immunostimulatory mediators by activated macrophages may be an important contributing factor, rather than disarrangements caused by long-standing glucocerebrosidase accumulation. In theory, early enzyme replacement therapy initiation may prevent antigenic stimulation and cytokine production, and reduce hyperimmunoglobulinemia and lymphatic neoplastic diseases in patients with type 1 Gaucher disease.