We have used a method [Gunning et al., Mol. Cell. Biol. 3 (1983) 787-795] of cDNA clone isolation from a cDNA library that selects for clones corresponding to abundant mRNAs and simultaneously yields a large number of different cDNA clones containing a high fraction of nearly full-length inserts. We screened an adult human skeletal muscle (skm) cDNA library and have isolated 46 cDNA clones which correspond to different mRNAs expressed at significant levels in adult skm. Of these cDNA clones 17 appear to be muscle-specific. Eleven are expressed in both cardiac muscle and skm but six are expressed primarily in skm. The remainder are expressed in muscle as well as in human fibroblasts. Comparison of cDNA insert size with mRNA size for the 17 clones expressed only in skeletal plus cardiac muscle revealed that eight are full-length, five are not and four recognize multiple transcripts which prevent a definitive conclusion. These cDNA clones will greatly facilitate the characterization of genes which are regulated during human muscle development.