The synaptotagmin gene family currently includes 12 members, Analysis of the three known genomic synaptotagmin sequences reveals conserved exon-intron patterns which delineate the synaptotagmin structural domains. We used expressed sequence tag, reverse transcription PCR and RNAse protection assay analysis of synaptotagmin messenger RNAs to demonstrate the occurrence of alternative splicing events involving a number of exons. Exon-skipped messages where transmembrane sequences have been removed or altered were found to be abundantly expressed by synaptotagmins 1, 4, 6 and 7, Although the expression of most synaptotagmins predominates in neural tissue, we find that by contrast, synaptotagmin 6 is more abundant in thymus, (C) 1999 Federation of European Biochemical Societies.