Two novel membrane disintegrin-metalloproteases, ADAM 20 and ADAM 21 were cloned from a human testis cDNA library. Their predicted translation products share 50% sequence identity with each other. Among previously characterized ADAMs, the best similarity was to sperm cell-specific fertilins-alpha and -beta, and meltrin-gamma (ADAM 9) which is ubiquitously expressed. Both ADAM 20 and 21 mRNAs are exclusively expressed in testis, presumably, in analogy to all other testis-specific ADAMs, on mature spermatocytes. Both cDNAs were mapped on the genome, and found to be tightly linked to the same marker (SHGC-36001) on chromosome 14q24.1. This region is not syntenic with the loci of mouse sperm-specific ADAMs 1-5. ADAM 20, but not 21, encodes a consensus Zn2+ binding site of active adamalysin metzincin metalloproteases, and both 20 and 21 encode putative cell-fusion peptides, required for sperm-egg fusion. Based on these characteristics it is possible that ADAM 20 and/or 21 is the functional equivalent of sperm fertilin-alpha, as it was recently reported that this gene is non-functional in humans.