Experiments were performed using an anaesthetised rat model to investigate the local inflammatory responses produced by intradermal injections of crude venom gland extracts from a number of Australian spiders, namely, Phonognatha graeffei, Delena cancerides, Isopeda montana, Badumna insignis, Lampona cylindrata, Steatoda grossa, S. capensis Hann. All of the venom gland extracts tested, with the exception of that from S. capensis, produced increases in vascular permeability consistent with acute inflammatory responses. The responses primarily involved the activation of 5-HT receptors, since they were markedly reduced by the nonselective 5-HT1/5-HT2-receptor antagonist methiothepin. Some of the venoms caused liberation of endogenous mediators of inflammation, and some had components that acted directly on the vasculature to increase vascular permeability. Histamine appeared to have little if any role in the observed increases in vascular permeability following intradermal injection of the spider venoms.