Cross-linking of electrospun (e-spun) fibre mats (beaded fibre morphologywith the average diameter of the fibre segments between beads being∼108 nm) of poly(vinyl alcohol) (PVA) containing sodium salicylate (SS), used as the model drug,was achieved by exposing the fibre mats to the vapour from 5.6 M aqueous solution of eitherglutaraldehyde or glyoxal for various exposure time intervals, followed by a heat treatmentin a vacuum oven. With increasing the exposure time in the cross-linking chamber, themorphology of the e-spun fibre mats gradually changed from a porous to dense structure.Both the degree of swelling and the percentage of weight loss of the cross-linked fibre mats(i.e. ∼200–530% and ∼15–57%, respectively) were lower than those of the untreated ones(i.e. ∼610% and ∼67%, respectively). Cross-linking was also responsible for the monotonic increase in the storagemoduli of the cross-linked SS-loaded e-spun PVA fibre mats with increasing exposure timein the cross-linking chamber. The release characteristic of the model drug fromthe SS-loaded e-spun PVA fibre mats both before and after cross-linking wasassessed by the transdermal diffusion through a pig skin method. The cumulativerelease of the drug from these matrices could be divided into two stages: 0–4 and4–72 h, in which the amount of SS released in the first stage increased very rapidly,while it was much slower in the second stage. Cross-linking slowed down therelease of SS from the drug-loaded fibre mats appreciably and both the rate ofrelease and the total amount of the drug released were decreasing functions ofthe exposure time interval in the cross-linking chamber. Lastly, the cross-linkedSS-loaded e-spun PVA fibre mats were non-toxic to normal human dermal fibroblasts.