The total serum activity of γ-glutamyl transpeptidase (GGT) was shown to increase with the growth of transplantable B16 and S91 melanomas in inbred mice. In an effort to define the source of the GGT shed into the bloodstream the physicochemical characteristics of the partially purified GGT isoforms from liver, serum and B16 melanoma were compared. The molecular weights of the serum and melanoma isoforms were identical (86 kDa) and differed from that of the liver isoform (69 kDa). In polyacrylamide gel electrophoresis the serum and melanoma isoforms had a similar mobility which exceeded that of the liver enzyme. Treatment of the enzyme preparations with neuraminidase removed the differences in the electrophoretic mobility of the three GGT isoforms studied. On ion exchange chromatography on a DEAE-Spheron 300 LC column the melanoma and serum isoforms had an affinity to the sorbent unlike the liver isoform. Our observations suggest that melanoma cells express a sialoform of GGT which is responsible for an increase in the total GGT serum activity. Biochemical and histochemical analyses did not reveal any increase in liver GGT production associated with melanoma development. Detection of the GGT isoform of tumour origin in sera ranks GGT among the specific melanoma markers. © 1998 Rapid Science Ltd.