Serum levels of four acute phase proteins, alpha 1-acid glycoprotein (AAGP), alpha 1-antitrypsin (AAT), haptoglobin (Hpt), and C3, were measured prior to biopsy in 38 women subsequently shown to have Stage I and II breast cancer and prior to treatment in 16 women with Stage IV disease. Sixty-one women with benign and 28 women with no breast disease served as controls. Mean serum levels of all four proteins were significantly elevated in women with stage IV disease as compared to women with Stage I or II disease or controls. Normal versus elevated levels for each protein were defined and AAGP was found to be the single most sensitive predictor of disseminated disease among the four. AAGP was elevated in 81.3% of Stage IV, 25% of Stage II, 14.3% of Stage I, and 12.4% of controls. Women with multiple proteins elevated were most likely to have advanced stage disease. Composite analysis of all four proteins using number of proteins abnormal or logistic regression analysis gave results similar to AAGP, both showing increasing numbers of proteins abnormal with increasing stage of breast cancer. These results indicate that measurement of serum acute phase proteins may be useful in initial staging of breast cancer patients and in following patients for indications of disseminated disease.