Synapsin III, the most recently described member of the synapsin gene family, displays a gene structure and protein domain structure similar to those of synapsins I and II. In this report, however, we describe major differences in the temporal- and tissue-specific expressions of synapsin III. Whereas synapsins I and II each give rise to two isoforms that are expressed predominantly in adult brain, there are at least six synapsin III transcripts (synapsin IIIa-IIIf) that differ with respect to tissue- and developmental stage-specific expression. Three of the neuronal transcripts are detected in fetal and to a lesser extent in adult brain (IIa-IIIc), whereas one (IIId) is detected only in fetal brain. Two additional transcripts (IIIe and IIIf) are detected only in nonneuronal tissues. A putative second promoter, which is contained within an intron in the synapsin III gene locus, appears to generate the nonneuronal synapsin IIIe and IIIf transcripts. This level of genome complexity is far greater than that described previously for the synapsin I and II genes and suggests that synapsin III may have functions distinct from those described for synapsins I and II.