Light and electron microscopy revealed a series of structural changes that occur in the fat body of the tobacco hornworm, Manduca sexta, during the fifth, i.e. the final, larval stadium. At each developmental stage studied, the cells of the fat body were homogeneous in structure. We found no evidence suggesting the presence of more than one type of fat body cell. Our structural data are consistent with published observations on biochemical activities of M. sexta fat body at particular developmental stages. Specific points of agreement include: (a) acquisition of Golgi complex (GC) and rough endoplasmic reticulum (RER) concomitant with the time of major protein production; (b) loss of many cellular organelles (such as GC and RER) as protein production drastically decreases; (c) accumulation of protein granules and urate granules after the onset of wandering (i.e. during the pre-pupal period); (d) accumulation of lipid and glycogen throughout the feeding period. In addition we found that (a) the plasma membrane reticular system (PMRS) developed during the period when protein secretion was great; (b) the PMRS was lost abruptly at the onset of wandering; and (c) the nucleus changed in shape from being roughly spherical to elliptoid in the pre-pupal stage. We found that the structure of M. sexta fat body is similar to that published for other Lepidoptera. However, it differs from that of Heliothis zea in that regional differences are not obviously apparent.