Neuraminidase deficiency has been demonstrated in cultured skin fibroblasts of patients who have adult type sialidosis with partial beta-galactosidase deficiency. A substantial amount of residual enzyme activity has been observed in leukocytes, however. To explain this discrepancy, the nature and distribution of the enzyme were studied. Neuraminidase activity was higher in lymphocytes than in granulocytes of normal controls. In patients' lymphocytes, neuraminidase activity was profoundly decreased and total sialic acid contents were increased 2.3-fold. Two neuraminidases, one sonication-labile and the other sonication-stable, were found in lymphocytes; the former was predominant in cultured skin fibroblasts. The defective enzyme in this disorder was found to be the sonication-labile neuraminidase in both cultured skin fibroblasts and lymphocytes.