The effect of CMF adjuvant therapy (cyclophosphamide, methotrexate, and 5-fluorouracil) on endocrine function was investigated in breast cancer patients. CMF therapy resulted in suppression of ovarian function in some premenopausal patients but pituitary function and adrenal function were unaffected. There was an inverse relation between age and duration of treatment required to induce ovarian suppression. Although amenorrhea was achieved within 2-4 months in patients aged 40 years or older, younger women required larger cumulative doses of cytotoxic drugs to induce ovarian dysfunction. Patients younger than 30 years of age continued to menstruate with no major alteration in hormonal levels resulting from the cytotoxic drugs. CMF therapy had no significant effect on hormonal levels in postmenopausal patients indicating that in this group therapeutic response is not mediated via the endocrine system.