Neurons in the medial septum (MS) and vertical limb of the diagonal band (vDB) undergo degenerative changes following transection of their axons. These changes have been well studied by histological techniques such as Nissl stains and immunocytochemistry. A dramatic loss of stained neurons occurs following axotomy and this has been interpreted as indicative of neuronal death. However, since the staining intensity and the size of affected neurons may be reduced by axotomy, it is possible that the apparent neuronal death may actually be due to a decrease in somal size or the ability to detect neurons by routine histological methods. The present study describes the effects of axotomy on MS and vDB neurons which have been labeled by hippocampal injections of the retrograde tracer, Fluoro-Gold (FG), prior to transection of the fimbria-fornix and supracallosal stria. The number of FG-labeled neurons in the MS decreased by 21% at three weeks, 36% at six weeks, and 31% at ten weeks after fimbria-fornix transection. The reduction was statistically significant at 6 and 10 weeks. The number of FG-labeled neurons in the vDB showed no reduction at three weeks but was decreased by 31% and 37% at six and ten weeks, respectively. This was statistically significant only at 10 weeks. By comparison, the number of neurons immunoreactive for choline acetyltransferase (ChAT) was reduced by 75-80% at these time points. The size (area and diameter) of FG-labeled somata decreased in both the MS and vDB within three weeks following fimbria-fornix transection and remained relatively constant at the six- and ten-week time points.(ABSTRACT TRUNCATED AT 250 WORDS)