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Combined oral contraceptives may alter the microenvironment of the female genital tract and, thus, influence susceptibility of endocervical cells to HIV-1 transmission. The mechanism for this effect is unknown but might involve combined oral contraceptive up-regulation of chemokine receptors on CD4+ endocervical cells. We measured chemokine co-receptor (CCR5 and CXCR4) expression on cervical intraepithelial CD4+ T lymphocytes, macrophages and dendritic cells using flow cytometry in 32 healthy women, 16 of whom were combined oral contraceptive users and 16 non-users. All women tested negative for sexually transmitted infections. Combined oral contraceptive users showed a higher proportion of CCR5+ CD4+ T lymphocytes compared with combined oral contraceptive non-users (P < 0.05). However, expression of both co-receptors on cervical intraepithelial macrophages and dendritic cells was no different between the two groups. Up-regulation of CCR5 on cervical intraepithelial CD4+ T lymphocytes offers a potential explanation by which women receiving combined oral contraceptives may be at increased risk of HIV transmission.