The present study is the first report on the bioactivity of venom from the Australian theraphosid spider Selenotholus foelschei. Venom from female specimens was used in all experiments. Adult spiders yielded an average of 2.2 mg dried venom per milking with a maximum yield of 7.2 mg. To evaluate the activity of pooled S. foelschei venom in invertebrates, a toxicity test in crickets (Acheta domesticus) was used. The results suggest the presence of several insecticidal toxins with different but synergistic modes of action, leading to a fast onset of paralysis as well as persistent paralysis and lethal effects (starting at 4 h after injection) in crickets. Vertebrate activity of S. foelschei venom was tested by using the isolated chick biventer cervicis nerve-muscle preparation. The venom produced a significant reduction in baseline tension (at a concentration of 10 microg/mL) and twitch height (at 0.2-10 microg/mL). Twitches were not restored after repeated washing. The response of the muscle to exogenous acetylcholine (1 mM) and carbachol (0.02 mM) was not reduced by the venom. These results indicate the presence of a vertebrate-active neurotoxin in S. foelschei that irreversibly blocks muscle twitches by acting either on voltage-activated Na(+)-channels or on other pre-synaptically located receptors.