The children's ages range from three years old to just a few days.
They were found at a house in Antigua, close to the capital, after neighbours reported seeing foreigners collecting children there every day.
Police are investigating whether the children were stolen, or their parents were coerced into giving them up.
Last year, couples in the US adopted more than 4,000 infants from Guatemala, second only to China.
The Guatemalan attorney general's office said that few of the children had the necessary paperwork to be in the custody of anyone other than their parents, and the house did not have permission to operate as an adoption centre.
The 46 children have remained at the house, being looked after by police, while the case is being investigated.
Latin America correspondent Daniel Schweimler says adopting from Guatemala can take half the time and cost considerably less than it does elsewhere.
Earlier this year, the Guatemalan Congress ratified The Hague Convention on Inter-country Adoptions which sets out a series of measures guaranteeing greater transparency in the process of adoption
However, the US state department is advising against the practice because of reports that many Guatemalan mothers face pressure to sell their children into adoption.
Last week, the US embassy in Guatemala tightened up the visa regulations for couples trying to adopt there.
Guatemala-based journalist Martin Asturias told the BBC that adoption had become big business in the country.
Prices range from around $25,000 (£12,500) up to about $60,000 (£30,000) depending on how complicated the process was and how specific the adoptive parents were in their demands, he said.
The business of adoption has also had a wider effect, Mr Asturias said.
"Guatemala has fallen into what I would say is a 'social psychosis'.
"Rumours can spread, especially in small Mayan villages or towns, that children are being stolen to be sold as adopted children."
The anxiety and anger caused by such rumours have in the past led to people believed to be involved in the adoption business being lynched or stoned, said Mr Asturias.
In a separate development, on Friday, 47 Haitian children whose parents gave them to traffickers in return for promised financial help were rescued, the International Organization for Migration (IOM) said.
The children, aged between two and seven, were freed from a rogue adoption centre in the Caribbean country's capital, Port-au-Prince, following government intervention.
The IOM said the children are offered to rich Haitians and foreigners in return for money.
Last Mod: 13 Ağustos 2007, 15:34