Various lines of evidence suggest that a polymorphism in the gene for proopiomelanocortin, Pomc1, might account for some portion of the genetic variance for open-field activity in the LS x SS RI strains. To test this hypothesis, approximately 1600 bp of Pomc1 was sequenced from genomic DNA of seven of the LS x SS strains. Two distinct alleles containing a total of five single-base pair differences were detected. A substitution was found in the coding region causing a Pro-to-Ser conversion, two substitutions occurred in the 3' untranslated region of the mRNA, and a substitution and a deletion were detected in the 3' untranscribed flanking region. The fragment containing the coding region substitution was sequenced in an additional 15 of the LS x SS strains. A total of 12 strains contained one form of the allele, while 10 had the other. The strain distribution pattern of open-field activity scores between the two allels suggests that these alleles do not contribute to the genetic variation of open-field activity in the LS x SS RI strains.