The surfactant, pulmonary-associated protein C (SFTPC) is a peptide secreted by the alveolar type II pneumocytes of the lung. We have characterized the porcine SFTPC gene at genomic, transcriptional, and protein levels. The porcine SFTPC is a single-copy gene on pig chromosome 14. Two transcripts were found in a newborn pig lung cDNA library: a full-length clone and a clone missing exon 5. cDNA sequence comparison revealed four synonymous and two nonsynonymous substitutions and in-frame insertions at the beginning of exon 5. Comparison of the SFTPC coding region between several mammals showed high levels of conservation. Northern blot studies showed lung-specific expression of the full-length SFTPC transcript, appearing in 50-day-old fetus and increasing during lung development. Both SFTPC transcripts were detected mainly in lung by real-time RT-PCR and they were significantly down-regulated in necrotic lungs of pigs infected with Actinobacillus pleuropneumoniae. Additionally, the protein levels were also decreased or absent in the necrotic tissue.