Telomerase is expressed in approximately 90% of breast cancers but not in normal somatic cells. The catalytic subunit of telomerase, human telomerase reverse transcriptase (hTERT), is a widely expressed tumour-associated antigen against which specific cytotoxic T lymphocyte (CTL) responses have been identified. Human CD8+ CTL have been shown to recognise hTERT synthetic peptides in an HLA-restricted manner and to lyse hTERT+ tumour cells. This study has investigated the specific CD8+ CTL response in a defined cohort of primary breast cancer patients against 3 hTERT peptides using an IFNgamma ELISpot assay. A specific CD8+ CTL response against at least one of the hTERT peptides was observed in 75% of cancer patients, with 8/17 patients responding to both HLA-A2 restricted peptides. In contrast, 38% of normal healthy female controls responded against a single peptide only. This suggests that a specific immune response exists against hTERT in breast cancer patients and that hTERT is a suitable target for tumour-based immunotherapy.