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 greater than 0.1). However, a significant association was found between cathepsin D and p29 (Fisher's exact test, P less than 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 less than 0.05). This association was more significant in tissues expressing estrogen and progesterone receptors as well as p29 (P less than 0.001). In contrast, cathepsin D synthesis was not related to tumor size, lymph node involvement, or patient's age (P greater than 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 less than 0.001).