We compiled a comprehensive database of alternative exons from the literatu
re and analyzed them statistically, Most alternative exons are cassette exo
ns and are expressed in more than two tissues. Of all exons whose expressio
n was reported to be specific for a certain tissue, the majority were expre
ssed in the brain. Whereas the length of constitutive exons follows a norma
l distribution, the distribution of alternative exons is skewed toward smal
ler ones. Furthermore, alternative-exon splice sites deviate more from the
consensus: their 3' splice sites are characterized by a higher purine conte
nt in the polypyrimidine stretch, and their 5' splice sites deviate from th
e consensus sequence mostly at the +4 and +5 positions. Furthermore, for ex
ons expressed in a single tissue, adenosine is more frequently used at the
-3 position of the 3' splice site, In addition to the known AC-rich and pur
ine-rich exonic sequence elements, sequence comparison using a Gibbs algori
thm identified several moths in exons surrounded by weak splice sites and i
n tissue-specific exons, Together, these data indicate a combinatorial effe
ct of weak splice sites, atypical nucleotide usage at certain positions, an
d functional enhancers as an important contribution to alternative-exon reg
ulation.