We have determined the nucleotide sequences of the 5' noncoding regions and the regions encoding the first 56 amino acids of rat and porcine pro-opiomelanocortin (POMC) mRNA. We accomplished this by sequencing cDNA produced by elongating specific DNA primers hybridized to neurointermediate pituitary mRNA. The nucleotide sequence of the 5' region of rat POMC mRNA fills a gap in our knowledge of the structure of this mRNA and the protein it codes for. While we have observed only a single porcine POMC mRNA, two different rat POMC mRNAs are detected. The rat POMC mRNAs differ by a 30-base insertion/deletion in their 5' noncoding regions. Its position and sequence suggest that it is the result of alternate modes of intron removal during RNA splicing.