This study investigated 51 patients with Type 1 Gaucher's disease clinically and radiographically for the presence of osteonecrosis. Twenty-five female and 26 male patients with a mean age of 37 years were evaluated retrospectively for osteonecrosis of the proximal and distal femur, proximal tibia, and proximal humerus. All patients were examined before enzyme replacement therapy. Gender, age at diagnosis, prior splenectomy, hematocrit, platelet count, acid phosphatase level, radiographs of the long bones, and magnetic resonance quantitative chemical shift imaging of the spine were analyzed to see if any of these values or findings were associated with the presence of osteonecrosis. Splenectomy was an independent risk factor for the presence of osteonecrosis in three of the four major sites and was a multivariate risk factor for osteonecrosis of the proximal femur and tibia. Male gender was the other significant multivariate risk factor for osteonecrosis of the humerus and distal femur when all sites were taken into account.