Prostate-specific antigen (PSA) is believed to be a highly specific marker for normal or cancerous prostatic tissue. We recently found that immunoreactive PSA (IR-PSA) is present in 30% of breast tumor cytosols (from 525 breast cancer patients). In this paper we analyzed a new series of 750 breast tumor cytosols, obtained from 744 women and six men, for IR-PSA. The positivity rates in the old and new series were very similar (approximately 30%). Combining the two series of breast cancer patients, we examined the associations between IR-PSA and estrogen (ER) or progesterone (PR) receptors, or patient age. We found that IR-PSA positivity rate declines with age. PSA-positive tumors were highly associated with either ER-positive or PR-positive tumors alone. However, analysis in a subset of tumors that combine the two receptors, ER(-)/PR(-), ER(+)/PR(-), ER(-)/PR(+), and ER(+)/PR(+), revealed that IR-PSA was only associated with PR, and no relationship was found between IR-PSA and ER. We speculate that the presence of IR-PSA in breast cancer may be associated with the PR action and that the association between PSA and ER is indirect due to the known association between ER and PR. As five of the six male breast tumors were found negative for IR-PSA, it is suggested that androgen may not be involved in the presence of IR-PSA in breast tumor.(ABSTRACT TRUNCATED AT 250 WORDS)