Background and aim of work : Colorectal cancer (CRC) is one of the most common malignant neoplasms.Glutathione-s-Transferase enzyme (GST) protects the colorectal mucosa through detoxification of carcinogens. The aim of the present study is to investigate the role of plasma total activity of GST in the development and its diagnostic potential for colorectal cancer in comparison with non-neoplastic gastrointestinal (GIT) lesions versus control subjects.Patients and methods : The mean plasma GST activity was assayed spectrophotometrically in 40 patients with CRC (group 1), 17 patients with benign colorectal lesions (group 2) and 18 apparently healthy individuals (group 3).Results : The mean GST activity was higher in 90% of CRC patients above the mean±2SD (19.4 nmol/min./ml.) of the contol group.However,some overlap exists between malignant and benign groups. Only 7 (17.5%) out of 40 cases with CRC had values far higher than benign lesions group with no overlap.6 of them were found to have cancer in the sigmoid and left colon and one case had left colon cancer with hepatic metastases. Conclusions : Measurement of the total plasma GST activity is not sufficiently sensitive to differentiate between malignant and benign cases while measurement of the GST classes (alpha, mu and pi) which are reported to be present in the colon, especially pi being the predominant isoenzyme in malignant tissues may be more helpful.Also, cases with benign colorectal lesions having a high plasma GST activity may need close follow up by colonoscopy and biopsy for the possibility of malignant transformation.