Seventy-three primary human breast cancers were analyzed to assess the presence of estrogen and progesterone receptors, the p29 protein, and the total cathepsin D status. No significant relationship was found between cathepsin D concentration and the presence of ER or PR, either by Fisher's exact test or Spearman's rank correlation (P > 0.1). However, a significant association was found between cathepsin D and p29 (Fisher's exact test, P < 0.001) and between cathepsin D and steroid receptor status in samples expressing both estrogen and progesterone receptors (positive by steroid binding assay and enzyme immunoassay) (P < 0.05). This association was more significant in tissues expressing estrogen and progesterone receptors as well as p29 (P < 0.001). In contrast, cathepsin D synthesis was not related to tumor size, lymph node involvement, or patient's age (P > 0.05). Steroid receptors and cathepsin D were also assayed in samples of non-malignant tissue from 16 mastectomies; there was a significantly higher relative concentration of cathepsin D in the malignant specimens (Student's t-test, P < 0.001).