We have shown previously that IgG antibodies in certain pemphigus sera, particularly endemic Brazilian pemphigus foliaceus (BPF) sera, react with bovine desmocollins (Dsc), which are transmembranous glycoproteins of desmosome junctions. Desmocollins occur as three different isoforms (Dsc 1, 2 and 3), all of which are represented in the epidermis. In this study, we examined sera of various pemphigus types by immunoblotting purified bovine desmosomes and bovine Dsc 1, 2 and 3 fusion proteins, expressed in pGEX expression vectors. Six of 15 (40.0%) BPF sera, two of 18 (11.1%) non-endemic pemphigus foliaceus sera, eight of 39 (20.5%) pemphigus vulgaris (PV) sera, and two of 11 (18.2%) normal sera, showed reactivity with Dsc from desmosomes. Experiments with fusion proteins showed that no Dsc isoform was specifically recognized by sera of any individual pemphigus type. Our results indicate that the pathogenesis of pemphigus might be more complex than previously believed.