We studied a total of 61 cases of systemic and senile amyloidosis to evaluate the significance of a "hyposplenic blood picture" (the presence of numerous Howell-Jolly bodies) in these patients and to correlate its presence with the pattern and severity of the splenic involvement. To ascertain whether this peripheral blood picture is prevalent with a certain type of amyloidosis, we classified all cases by immunostaining with a panel of antibodies against AL amyloid (kappa and lambda light chains), serum amyloid-associated protein, prealbumin, beta-2 microglobulin, and amyloid p component. Based on immunostaining results, all cases were classified as AL (31 cases), AA (8 cases), or senile (prealbumin-positive, 22 cases) amyloidosis. Howell-Jolly bodies were identified in six patients with amyloid L amyloidosis; of these, four cases had diffuse splenic cord involvement, one had a follicular pattern, and one had a vascular pattern. Only one of these patients had a typical hyposplenic blood picture. This patient had far-advanced diffuse splenic involvement. The remaining five patients had rare to few Howell-Jolly bodies. In addition, 12 other patients had diffuse splenic involvement with no Howell-Jolly bodies present. This study concludes that even when there is advanced diffuse replacement of splenic cords with amyloid on light microscopy, the "pitting" function of the spleen appears to be preserved in most cases. The absence of a hyposplenic blood picture cannot be equated with normal splenic cord histology in patients with systemic amyloidosis.