Plasma levels of carcinoembryonic antigen (CEA) and the 15,000 molecular weight gross cystic disease fluid protein (GCDFP-15) were determined in 30 patients with metastatic breast carcinoma before, during, and after treatment with fluoxymesterone. Within 2 weeks after initiation of treatment, plasma levels of GCDFP-15 increased 50% above basal values in 15 (79%) of 19 patients. Similar increases in plasma CEA levels occurred in only 5 (23%) of 22 patients. Eight (33%) of 24 patients achieved increases in GCDFP-15 of 500% or more above basal levels after 14-336 days of therapy. Within 2 weeks of fluoxymesterone termination, 14 (93%) of 15 patients had a decrease in plasma GCDFP-15 levels, and in 12 (80%) the decrease exceeded 33% (the inverse of a 50% increase). Conversly, only 5 (33%) of 15 patients experienced a decrease in plasma CEA levels within 2 weeks of therapy termination, and in only 1 (6.7%) subject did the decrement exceed 33%. Nine (90%) of 10 patients who had 50% increases in plasma GCDFP-15 during initial androgen therapy also had significant decreases in plasma GCDFP-15 following termination of therapy. Data on 3 prospectively studied patients demonstrated that plasma GCDFP-15 rose within 24 hours of initiation of fluoxymesterone therapy and continued to rise for at least 6 days. Increased plasma levels of GCDFP-15 were reflected in increased urinary excretion of the glycoprotein.