The venom of Cupiennius salei consists of many low molecular compounds, nine neurotoxic acting peptides (CSTX), at least eight neurotoxic and cytolytic acting peptides (cupiennins), a highly active hyaluronidase, and several hitherto unidentified proteins. The structure of several peptides is given. A synergistic action between three main groups is proposed: injected into the prey tissue, the enzyme hyaluronidase acts as a spreading factor, thus, facilitating a better access of venom neurotoxins to their targets, cupiennins disturb cell membranes and influence cell excitability, through this augmenting the mere neurotoxic effect of CSTX-1 synergistically. The venom glands of an apocrine secretion type provide an average of 12 microl per milking (adult female). Venom sensitivity of arthropods differs between 0.001 and >20nl venom/mg insect. Regeneration time of an empty venom gland is approx. 2 weeks. Consequently, spiders may encounter situations in which they have to decide whether their limited venom storage is sufficient to kill a given prey item. Experiments are presented which show that C. salei knows the actual venom content of its venom glands. It injects no more venom than necessary. This coincides with an experimentally determined LD(50) value in harmless prey items, but C. salei injects more venom in aggressive or otherwise dangerous prey items (quantification of injected venom amounts by monoclonal antibodies). These results indicate that C. salei uses its venom as economically as possible and this supports our venom optimisation hypothesis.