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Hundreds of Sepia officinalis were hatched and cultured through the life cycle in each of 13 populations. Two genetic lines were maintained: one for an unprecedented seven generations and another presently in its fourth. All generations—save one—produced animals in excess of 1·0 kg body weight. Seven of eight generations with adequate data records had mean weights of 1–2 kg, and the largest cuttlefish reared were a male 2·6 kg and a female 2·9 kg. Fecundity levels were high, but there was a trend towards decreased fertility in later generations, with fertilization rates dropping below 10%. In the 7th generation, most mature animals failed to engage in agonistic courtship and mating behaviour. Almost no normal eggs were laid and none was fertile, thus ending the lineage. Most culture took place at 20–24°C and temperature generally explained variations in life span duration: being of shorter length at higher temperatures. Life spans were consistently longer at 20°C and sizes were greater than predicted from previously published literature. In both lines there was a trend towards larger individuals and longer life spans in subsequent generations. Survival of hatchlings typically exceeded 90% for two months post-hatching, and survival averaged 50% or higher to sexual maturity when corrected for animals removed from the populations for experimental use.