Serum immunoglobulin concentrations were determined in 21 patients with sickle cell disease syndromes and correlated with the size and visualization of the spleen. Whereas serum immunoglobulin A (IgA) levels were elevated in all patients studied, immunoglobulins G (IgG) and M (IgM) were elevated in those patients with demonstrable increase in splenic mass. When even minimal splenic visualization could be demonstrated, serum IgM was normal. However, when there was complete absence of splenic vi-sualization, or following splenectomy, serum IgM concentration was significantly below normal. This finding of low serum IgM concentration may explain the increased susceptibility to infection observed in some groups of patients with sickle cell disease.