The distribution of acid phosphatase (AP) in neuroepithelial cells in the embryonic hindbrain of the C57BL mouse was determined by means of ultrastructural cytochemistry. Fixed tissues were incubated in Gomori medium containing Na-beta-glycerophosphate as substrate and were post-fixed in osmium tetroxide, routinely dehydrated, and embedded in Epon. At 8.5-11 days, the reaction occurred in apical, intermediate, and basal zones of the neuroepithelium, although many cells were unreactive. In AP-positive cells, reaction product could be seen in saccules and vesicles associated with the Golgi complex, in large ill-defined vacuoles resembling autolysosomes, and in smaller membrane-bound bodies. By 12 days, most cells were unreactive, but a densely concentrated reaction product filled some cell processes in the midventral marginal layer. In all regions studied, the AP reaction was sensitive to sodium fluoride. Treatment with saponin and Triton-X did not affect the pattern or extent of the reaction. The results indicate that a change occurs in the nature of the AP reaction coincidental with differentiation between the eleventh and twelfth day, and that ultrastructural cytochemistry provides a means for further analysis of modifications in the distribution of AP during even earlier stages of neural development.