OBJECTIVES:   To investigate the prescribing cost of products classified as enzymes in a South African private health care insurance claims database over a two-year period.  METHODS:   A medical claims database for 2010 and 2011 of approximately 4.5 million records was analysed retrospectively.  All products classified as enzymes under the MIMS classification system were extracted for analysis.  RESULTS:   Enzymes constituted a very small percentage of medical insurance claims in this study (only 0.02% of approximately 4.5 million claims for products and procedures), yet they were relatively expensive.  Five different enzyme products were prescribed.  A total of 906 products (525 in 2010 and 381 in 2011) were prescribed at a cost of R1956948.76 (average cost of R2159.99; SD=R9929.54) over the two years.  Hyaluronidase was the most frequently prescribed (60.04% of all enzyme products), followed by pancreatin-containing products (34.66%).  The average cost per hyaluronidase prescription paid by the medical aids was R280.54.  The Single Exit Price (SEP) (unit price) of hyaluronidase on 12 January 2012 was R283.40.  Other enzymes prescribed were imiglucerase, alteplase and tenecteplase.  Imiglucerase was overall the most expensive (a cost of R58103.26 for the 200 units/5 ml vials and R62470.48 for the 400 units/5 ml vials prescribed).  The average cost of alteplase (recombinant human human tissue type plasminogen activator or r-tPA) was R6572.60 per prescription.  The amount claimed per tenecteplase injection was R11905.72 (8000 units) and R13091.24 (10000 units), respectively.  Streptokinase, regarded as the most affordable antithrombotic enzyme, was not prescribed.  Of the 579 patients who received one or more prescriptions for these products, 64.59% were between 40 and 69 years of age.  CONCLUSIONS:   These products are relatively expensive and warrant further pharmacoeconomic studies.  The importance of studies which include diagnoses and clinical parameters cannot be overemphasised.