The present study was undertaken with the aim of finding an alternative preservative system to methyl parahydroxybenzoate in zinc gelatin, which was described in the monographs of the Swiss Pharmacopoeia (until Ph. Helv. 8) and in previous editions of the German Pharmacopoeia (until DAB 7). This antimicrobial agent has now been withdrawn in the DAB, because of its potential allergy risks. As for the USP and DAB-DDR zinc gelatin preparations, they have always been devoid of any preservative agent, probably relying on the mild antimicrobial activity of zinc. A literature survey did not reveal if such an aqueous preparation containing the water-insoluble zinc oxide shows efficacious antimicrobial activity by itself. Thus, a comparative evaluation of differently preserved zinc gelatin preparations was performed using a test for the efficacy of antimicrobial preservation that has been modified with regard to the European Pharmacopoeia (EP) test to take into account the solid state of the preparations and the bactericidal effect of the zinc. Three zinc gelatin preparations were checked, either: (i), without any agent; or (ii), with 0.1% methyl parahydroxybenzoate; or (iii), with 0.5% phenoxyethanol, a broad-spectrum antimicrobial agent almost devoid of allergy risks. The three preparations behave quite differently, in particular with respect to fungi. All three preparations passed the modified EP test as far as bacteria are concerned. Even zinc gelatin without preservative is very effective, not only because of the mild antimicrobial activity of zinc (the soluble fraction of zinc oxide in the liquid phase of zinc gelatin was determined to be 13 microg/ml), but most probably because of the low water activity of the preparation (measured as around 0.81), as shown by the absence of growth of a zinc-resistant strain of Pseudomonas aeruginosa. Zinc gelatin preserved with methyl parahydroxybenzoate has a weak, although satisfactory, activity against Staphylococcus aureus. Regarding fungi, gelatin without an antimicrobial agent and that preserved with methyl parahydroxybenzoate meet the requirements for efficacy against Candida albicans, but are only bacteriostatic against Aspergillus niger. As for zinc gelatin preserved with phenoxyethanol, it displays the best activity against C. albicans and, above all, appears to be the only formulation exhibiting fungicidal activity against A. niger. It is therefore recommended to preserve zinc gelatin with this antimicrobial agent, as recently adopted in Supplement 2000 of the Swiss Pharmacopoeia.