Controversy exists in using carcinoembryonic antigen (CEA) for monitoring the clinical course of breast cancer. In this study, the kinetics of two plasma tumor markers, CEA and CA15-3, immediately after the initiation of chemotherapy were assessed in 30 patients with advanced breast cancer. Four distinct kinetic patterns were seen. Two patterns fitted the expected relationship where the plasma marker increased during tumor progression (nine patients), and declined in tumor regression (five patients). The third pattern was paradoxical in that objective tumor regression in eight patients was associated with an acute surge of these markers followed by a steady decline. The doubling times for both CEA and CA15-3 were immediately shortened four-fold after therapy suggesting tumor cytolysis in treatment responders. Equally paradoxical was the fourth pattern where tumor progression in eight patients was associated with a rapid and transient decline of markers followed by rebounds. Such a rapid decline may be due to a suppression of marker release, as demonstrated in an in vitro study. Adequate knowledge of these putative paradoxical patterns will permit their effective use in monitoring the disease course and perhaps in the early prediction of the therapeutic response.