260 patients with malignant disease received intravenous, intramuscular or intravesical hyaluronidase (H.) (Permease by Sanabo), 7,000 to 25,500 IU (10 to 30, 750 IU vials) or 200,000 IU (1 vial of H.) in addition to systemic or intravesical chemotherapy. Treatment was well tolerated except for 20 transient allergic episodes, 2 of which consisted in local symptoms at the injection site. Results are presented for 103 patients not responding to previous chemotherapy, 53 patients with primary and secondary brain tumours, and 51 patients with superficial bladder cancer. Adjuvant hyaluronidase was found to restore responsiveness in a large percentage of non-responders. The remaining systemically treated patients received H. together with their initial chemotherapy or with a modified cytostatic regimen. Intravesical H. in combination with mitomycin C was well tolerated and did not enhance mitomycin C plasma levels. In a randomized trial 5 of 23 patients with superficial bladder cancer receiving adjuvant intravesical mitomycin C alone developed tumour regrowth versus 1 of 21 patients receiving additional H. Adjuvant H. decreased 5-FU plasma saturation rates during arterial perfusion in colorectal cancer with metastatic spread to the liver, probably reflecting enhanced 5-FU extraction. Colorectal cancer stem cell assays with 5-FU showed a significant reduction of colony counts in the presence of H. Action mechanismus of hyaluronidase in malignant diseases are discussed, experimental data suggesting an effect of H. on immunologic events in malignant disease are presented.