Previous molecular genetic studies on channel catfish (Ictalurus punctatus) have focused on limited number of genes and gene products. Recent advancement of molecular techniques made high throughput analysis of transcriptomes possible. As part of our transcriptome analysis of channel catfish, we have analyzed 1909 expressed sequence tags (ESTs) derived from a skin library. Of the 1909 ESTs analyzed, 1376 (72.1%) ESTs representing 496 unique genes had homologies with other organisms while 478 (25.0%) ESTs had no significant homologies and were designated as unknown. The remaining 55 (2.9%) EST clones were eliminated because of their low quality or short sequences. Of the 496 unique genes, 327 (65.9%) genes were singletons while 169 (34.1%) genes represented by two or more ESTs. A total of 1007 (52.8%) ESTs representing 235 unique genes matched previously reported channel catfish ESTs while 847 (44.4%) ESTs representing 261 unique genes were newly identified from this research. Functional categorization of the channel catfish genes indicated that the largest group was ribosomal proteins with 65 unique genes represented by 500 clones. The most abundantly expressed gene, the calcium binding protein ictacalcin, accounted for almost 5% of overall expression, indicating its important function in the skin. Sequence analysis of ESTs revealed the presence of 89 microsatellite-containing genes that may be valuable for future mapping studies.