1. Irinotecan (also known as CPT-11) is a water soluble, semi-synthetic analogue of 20(S)camptothecin (CPT) with promising activity against a range of tumour types. 2. As with all other active analogues of CPT, irinotecan causes cell toxicity by stabilizing a ternary complex between the nuclear enzyme topoisomerase I (topo I) and double-stranded DNA. This leads to replication fork-arrest, double DNA strand breaks and, possibly, illegitimate recombination of vital genes. 3. This activity is much greater for its metabolite SN-38 and irinotecan is widely considered to be a prodrug of SN-38. 4. The anti-topo I activity of CPT is stereoselective at C-20 and irinotecan is synthesized from 20(S)CPT to ensure maximal activity. In aqueous solutions, the lactone ring of CPT undergoes reversible and spontaneous hydrolysis to a ring-opened and inactive carboxylate form. In patients, it has been shown that the lactone is the predominant form of SN-38 in plasma, whereas the opposite is true for irinotecan. 5. The transformation of irinotecan to SN-38 is catalysed by carboxylesterases. However, this conversion appears relatively inefficient in man. 6. Irinotecan and SN-38 show evidence of other metabolic reactions (type I and II), some of which could be subject to pharmacogenetic variability. 7. Therapy with irinotecan is associated with unusual toxicities, such as an acute cholinergic-like syndrome and delayed onset diarrhoea. Although the mechanism for the diarrhoea remains to be defined, the cholinergic toxicity appears to be due to an inhibition of acetylcholinesterase.