Summary Serum activity of ax-N-acetylgalactosaminidase (NaGalase), the extracellular matrix-degrading enzyme that appears to be produced exclusively by cancer cells, was measured in mice bearing SCCVII tumours (squamous cell carcinoma). The NaGalase levels in these mice increased with time of tumour growth and were directly proportional to tumour burden. After exposure of SCCVII tumours to a single X-ray dose of 20 Gy, the serum NaGalase levels gradually decreased during the first 10 days after treatment (to approximately one-third of the initial value) and then began to increase. The decrease in serum NaGalase activity was more rapid after the treatment of SCCVII and EMT6 tumours by photodynamic therapy (PDT) and was dependent on the PDT dose. The treatments (based on photosensitizers Photofrin or mTHPC) that were fully curative resulted in the reduction of NaGalase activity to background levels within 2 or 3 days after PDT. A slower decrease in NaGalase activity was found after PDT treatments that attain an initial tumour ablation but are not fully curative. The regrowth of PDT-treated SCCVII tumours was preceded by an increase in serum NaGalase levels, which was detected as early as 8 days before the visible tumour reappearance. These findings ascertain the validity of serum NaGalase measurement for the assessment of tumour response to different treatments and support the concept that the NaGalase measurement could serve as a diagnostic and prognostic index that might allow oncologists to design the dosage or nature of treatment.