The kinetics of avermectin disposition and metabolism in ruminant livestock and horses are reviewed with particular emphasis on the influence of route of administration and formulation on persistence of residues in tissues and excretion in faeces. Because information is not publicly available on other compounds in this class currently under development (e.g. moxidectin, doramectin), ivermectin only is considered. The biological half-life of ivermectin in plasma is similar in cattle and sheep but because of a larger volume of distribution, plasma clearance is more rapid in sheep. However, injection of the subcutaneous formulation of ivermectin prolongs plasma residence time and persistence of drug residues particularly in liver and fat. Increasing the organic solvent content of subcutaneous formulations slows the release of drug from the injection site and thereby prolongs its presence in the bloodstream. Because ivermectin and its metabolites are mainly excreted in bile, residues continue to appear in faeces for substantially longer following subcutaneous injection than after oral dosing. Aqueous based injectable formulations in cattle may therefore reduce the impact of ivermectin treatment on dung fauna. Binding of avermectins to digesta particulates during gut transit may potentially lower drug bioavailability and also contribute to faecal residues. Further research on formulation and dosage strategies is advocated to increase bioavailability at the gastrointestinal site of action so that both dose rate and faecal residues can be reduced.