Several breast carcinoma cell lines or explants of such tumors, as well as examples of lactating or dysplastic breast tissue, synthesized three serum proteins (alpha 2-Zn-glycoprotein, alpha 1-antichymotrypsin, and alpha-lipoprotein) in vitro. These proteins were detected by immunoperoxidase techniques in 126 breast carcinomas that had been evaluated clinically for more than six years. Alpha-2-Zn-glycoprotein was present in 58% of the carcinomas, whereas alpha 1-antichymotrypsin was seen in 55% and alpha-lipoprotein in 52%. These markers showed a relationship with clinical outcome. Alpha-1-antichymotrypsin and alpha-lipoprotein were unfavorable determinants, whereas alpha 2-Zn-glycoprotein was detected in lesions with a favorable evolution. Taken individually, these markers have similar but rather weak associations with five-year survival rates; roughly 20% of patients in the "favorable" group died, compared with 33% in the "unfavorable" group. Alpha-2-Zn-glycoprotein in grade 1 tumors was a marker with marginally favorable significance, but alpha 1-antichymotrypsin significantly worsened the prognosis of grade 2 and 3 tumors. Furthermore, stratification of patients according to the number of positive unfavorable markers yielded striking results. Eight percent of patients with none of the unfavorable markers were dead at five years, compared with 55% of those whose lesions expressed three unfavorable markers.