This study describes the sequence of the immunodominant Treponema pallidum surface protein TpD and its expression in Escherichia coli. The translated TpD DNA sequence revealed the presence of a putative site for lipid-modification downstream from the signal sequence of this membrane protein. Growth of TpD-expressing E. coli in the presence of radioactive palmitic acid revealed that TpD was lipid-modified. Three other, previously characterized cloned proteins of T. pallidum were also lipid-modified. The N-termini of two of three sequenced T. pallidum proteins contain a tetrapeptide sequence characteristic for lipoproteins in Gram-negative bacteria: Leu-X-Y-Cys. Only TpD differed from this consensus sequence in the substitution of the first residue by Phe. The apparent high incidence of lipoproteins among E. coli recombinants expressing T. pallidum antigens suggest an important role of lipoproteins in the induction of humoral immunity during syphilitic infection.