Natural chromosomal ends are stabilized by proteins that bind duplex telomeric DNA repeats. In human cells, the TTAGGG Repeat Factor 1 (TRF1) was identified by two independent studies, one screening for factors that bind duplex telomeric DNA^1,2 and the other screening for proteins containing a particular Myb motif called the telobox, which is required for telomeric repeat recognition (Fig. 1a; refs 3–5). A second human open reading frame, orf2, contains a telobox sequence and encodes a polypeptide that specifically recognizes mammalian telomeric repeat DNA in vitro³. We show that two proteins of 65 and 69 kD, expressed in HeLa cells, contain the orf2 telobox sequence. These proteins are collectively termed TRF2. Affinity-purified antibodies specific for anti-TRF2 label the telomeres of intact human chromosomes, strengthening the correlation between occurrence of telobox and telomere-repeat recognition in vivo.