The genetic basis of oligodontia, a severe form of tooth agenesis, is largely unknown.  The condition is typically transmitted as an autosomal dominant trait with variable expressivity.  Two genes MSX1 and PAX9 are known to be responsible for tooth agenesis.  Specifically, PAX9 has been identified as the cause for molar oligodontia in one large family (Stockton et al., 2000).  We subsequently identified a small family affected with a pattern of autosomal dominant molar oligodontia similar to that in the previously described family.  Objective:  The objective of our study was to determine if PAX9 was responsible for molar oligodontia in this family.  Methods:  We constructed a pedigree, performed radiographic analysis, and collected blood for DNA extraction from all family members.  PCR-based mutational analysis of the candidate gene PAX9 was performed for exons 2 to 4.  Multiple sequence alignment of Pax9 from 3 species and eight members of the Pax family was performed to determine evolutionarily conserved amino acid residues. Results:  Direct sequencing of PCR products revealed a missense mutation located at: A 260 T in affected individuals and not in unrelated controls.  The missense mutation resulted in an amino acid change from isoleucine to phenylalanine.  Our alignment of multiple Pax sequences revealed that isoleucine is highly conserved at this position.  Conclusions:  Taken together these results further confirm that a mutation in PAX9 is responsible for molar oligodontia in this family.  This investigation was supported in part by an AADR Student Research Fellowship (AJ), and by the AAOF (SF-B), UT-HSC (SF-B), THECB-ATP 00494901431999 (RDS), and NIH grant R01 DE13668 (RDS and SF-B).