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It is important that the animals you intend to breed are old enough and large enough. A male typically needs to weigh over 700 grams and be at least one year old. Evidence of maturity can be determined by expressing a sperm plug. Gentle pressure on the cloaca (the vent at the back of the snake) will produce a little white, cheesy matter that will tell the male is ready. While females as small as 1200 grams have been successfully bred, most breeders recommend that females be at least 3 years old and 1700 grams in order to breed. The process is too demanding on smaller animals and represents a health risk. It is best to be sure of the sex of the animals you intend to breed. This can be determined by probing. There are video tutorials available that teach the process. This can be dangerous to the animal, so do not probe a snake without first having received proper instruction; or call in an expert. Female snakes will probe to a depth of only 3 or 4 scales. Males will generally probe to 7-9 scales. It is possible to get a false positive for a female if the snake is constricting itself sufficiently to prevent the probe from achieving full penetration. In order to become fertile, a cooling-off period is required. The ambient air temperature at night needs to be in the mid 70's (F) low 20s (C) for a period of about a three months. The warm spot in the cage AT NIGHT should be reduced to low to mid 80's(F) low 30s (C), during the day temperatures should return to normal temperature in the high 80's(F). The idea is to replicate the weather conditions of winter in Central Africa. This short cool spell whispers sweet nothings into the brains of these beautiful creatures and tells them that Spring is coming and new life needs to be created. During the cooling off period, periodically introduce the male and the female. Have them together for a few days, then apart for a few days. They may try to breed at that time but it won't take. Still, it is a good sign. After the cool spell, the temperatures can be returned to normal. Good temperatures for ball pythons produces perspiration on most humans.
Make sure they have reached maturity before breeding. Determine the sex. Provide a cooling-off period. Warm it up again.