The circulating levels of a 90-kilodalton (K) tumor-associated antigen were measured in the blood of 43 patients with gynecologic and breast malignancies who underwent a short course of recombinant alpha-2b-interferon (rIFN alpha-2b) (3 million U/m2/d intramuscularly [IM] for 3 days). Of the 43 patients, 23 showed abnormal 90-K levels (greater than 1.7 U/ml). A significant increase of antigen levels was already observed 24 hours after the first administration and persisted throughout the investigation period. Of 20 patients with 90-K levels below the normal limit, 12 went over the normal cutoff value after two rIFN alpha-2b injections. No significant modifications of 90-K levels were detected in nine women receiving rIFN alpha-2b for the treatment of genital condylomata. The serum levels of two other tumor-associated antigens, CA 125 and CA 15-3, were not modified by rIFN alpha-2b administration. The ability of rIFN alpha-2b to increase the circulating levels of 90-K might have important clinical implications for the serodetection of cancer.