Tissue polypeptide antigen specific (TPS) was analysed in serum taken prior to chemotherapy in 90 patients with advanced gastrointestinal cancer and prior to every treatment course in 68 of these patients in order to explore whether serial tumour marker measurements can be of importance in monitoring patients treated with palliative chemotherapy. Elevated TPS levels were seen in 83/90 (92%) patients (48/52 colorectal, 9/9 pancreatic, 9/11 biliary, 17/18 gastric). Baseline TPS level correlated with performance status, tumour response and survival. Based upon the change in TPS levels after the first two courses in relation to baseline, a decrease by >50% had a high sensitivity for a favourable treatment outcome (partial remission and prolonged stationary disease (90%) or a subjective response (100%)), whereas the specificity was lower (72% and 73% respectively). A similar result was seen when the TPS levels were analysed at the time of the response evaluation after 2 months (sensitivity 91 and 95%, specificity 74 and 75% for an objective or subjective response respectively). In 7 out of 15 patients with an initially favourable outcome, an increase in TPS levels of >50% at two occasions was seen 8-20 weeks prior to clinical disease progression. In advanced gastrointestinal cancer serial TPS measurements can with high accuracy early identify patients who will not benefit from the treatment. On the other hand, a response must be confirmed using other methods in the presence of a decrease, since this was also seen in non-responding patients.