SUMMARY: Neural lobe neurosecretory granules (NSG) have been studied after different fixation procedures. When the pH of prefixation in a triple-aldehyde solution was varied, the dense core of NSG's was best preserved at pH's 5·0 and 6·0 but at pH's 7·0 and 8·0 loss of density of the granule core occurred and was most marked at pH 8·0. Increased duration of prefixation resulted in progressive loss of density of the granule core at pH's 7·0, 7·3 and 8·0, but at pH's 5·0 and 6·0 granules remained dense-cored, even after 24 h prefixation. When osmium tetroxide was used alone as a fixative, dense cores were again best preserved at acidic pH. This finding was correlated with studies in vitro in which the fixative solutions were reacted with aqueous suspensions of known components of the NSG's. The neural lobes of animals stimulated to release hormone by substitution of 2% NaCl solution for drinking water were also studied after fixation at different pH's. There was a significant decrease in the number of NSG's after treatment but no significant decrease in the proportion of NSG's which retained the dense-cored appearance at any pH. This suggests that hormone loss from the neural lobe is associated with loss of entire granules rather than with a reduction of density of the granule core and this finding is discussed in the light of theories on the mechanism of hormone release.