Growth and development of pig fetuses is dependent on the coordinated expression of multiple genes. Between 21 and 45 days of gestation, fetuses experience increasing growth rates that can result in uterine crowding and increased mortality. We used differential display reverse transcription-PCR (DDRT-PCR) to identify differentially expressed genes in pig fetuses at 21, 35, and 45 days of gestation. Pig cDNAs were identified with homologies to CD3 gamma-subunit, collagen type XIV alpha1, complement component C6, craniofacial developmental protein 1, crystallin-gammaE, DNA binding protein B, epsilon-globin, formin binding protein 2, ribosomal protein L23, small acidic protein, secreted frizzled related protein 2, titin, vitamin D binding protein, and two hypothetical protein products. Two novel expressed sequence tags (ESTs) were also identified. Expression patterns were confirmed for eight genes, and spatiotemporal expression of three genes was evaluated. We identified novel transcriptome changes in fetal pigs during a period of rapid growth. These changes involved genes with a spectrum of proposed functions, including musculoskeletal growth, immune system function, and cellular regulation. This information can ultimately be used to enhance production efficiency through improved pig growth and survival.