The nature and developmental profile of the soluble sialidase of rat forebrain were studied from birth to 150 days. Forebrain was extracted by two procedures, one (mild) preserving, the other (drastic) destroying nerve endings. The soluble extracts obtained by the mild procedure contained 64-78% of the total tissue cytosol, assayed as lactate-dehydrogenase; those obtained by the drastic procedure 87-94%. These latter extracts were considered as the soluble fraction containing 'all' tissue cytosol. The cytosolic origin of the sialidase contained in the soluble extracts at all examined ages was suggested by the following evidence: (a) during extraction sialidase behaved as lactate-dehydrogenase and quite differently from ?-hexosaminidase and ?-galactosidase, enzymes of lysosomal nature present in the same extracts, (b) the sialidase content of the extract was not influenced by the presence or absence of EDTA in the medium, (c) the sialidase content in the extracts did not diminish even after prolonged centrifugation (2 h) at high speed (150,000 g). The content of cytosolic sialidase referred to g fresh tissue increased from birth to 20 days, and slowly decreased thereafter. Till 20 days the content and the developmental trend of the cytosolic enzyme were similar to that of the better known membrane bound sialidase. This latter enzyme, however, reached its maximum at about 60 days of age. The specific activity of the cytosolic sialidase was lower till 10 days of age, higher from 10 to 30 days, and equalled that of the membrane bound enzyme during adult life. Therefore rat forebrain cytosolic and membrane bound sialidases, also from the developmental point of view, behave as different enzymes.