The circulating levels of a 90-kilodalton (KD) tumor-associated antigen were measured in the blood of 26 patients with ovarian cancer in clinical remission who received a short course of recombinant alpha-2b-interferon (rIFN-alpha-2b, 3 million U/m2/d intramuscularly for 3 days) before second-look procedures. The administration of rIFN-alpha-2b to 90-KD antigen-positive patients produced a slight increase of the marker. However, in patients without the marker but with evidence of disease, a remarkable increase above the cutoff level was observed. Less pronounced modifications of 90-KD antigen serum levels were found in patients with no disease at second look. Moreover, considering the 90-KD antigen mean percentage increase, the dynamic test with rIFN-alpha-2b was able to eliminate five of six false-negative results obtained with the 90-KD antigen basal assay alone. The sensitivity of the assay increased to 92% after IFN compared with 54% for the 90-KD antigen assay alone. An increase (greater than 100% above pretreatment titer) of 90-KD antigen levels during the test also was observed in four patients with no evidence of disease at second look. In two of these false-positive cases, recurrence of disease was observed 13 and 24 months later. At the time of this analysis, none of the patients with a negative second look and negative dynamic test had relapsed. These results suggest that the dynamic test with rIFN-alpha-2b might be a new tool to assess disease status in patients with ovarian cancer before second-look procedures.