The chances of dying early - below the age of 75 - are a fifth higher in the North of England compared with the South, research suggests.
A study published in the British Medical Journal said the north-south mortality difference was now at its widest for 40 years.
Researchers from the University of Manchester compared death rates from 1965 to 2008.
The government said health inequalities were being addressed.
In 1965, those living in the north were 16% more likely to die before the age of 75 than their southern counterparts. This had risen to just over 20% by 2008.
Men were more likely to be affected.
For men, the average geographical inequality rate over the period 1965 - 2008 was 15%, compared with 13% for women.
Lead researcher, Professor Ian Buchan, said that even when people in the North and the South were born into similar socio-economic groups, health inequalities persisted.
He said that this was because people in the South, even if they had low incomes, had greater access to resources: "There is an overall concentration of resource in the South, the 'built environment' is very different, there's more access to education, transport and other large scale resources."
Public health specialist Professor Sir Michael Marmot published an update to his in-depth review on health inequalities last week.
He said health inequalities are caused by social and economic reasons and that inequalities also existed within regions: "There is strong evidence that the underlying causes of the divide, the 'causes of the causes' are social and economic.
"For example, there is evidence that there are social gradients in health within every region; and that differences between neighbourhoods depend closely on their social and economic profiles.
"While these gradients exist within every region and local area, they are wider in the North."
Experts analysed trends for English government office regions, comparing the North with the South.
They looked at the North East, North West, Yorkshire and the Humber, East Midlands and West Midlands compared with the East of England, London, the South East and South West.
The researchers looked at the age of death across the whole population in each region they studied.
Overall, during that period, mortality in England has greatly reduced since 1965. It has reduced by about 50% for men and about 40% for women with both North and South experiencing similar reductions.
The gap between mortality rates in the North and South is now at its widest point, but it has fluctuated over the 43 years of the study.
From the early 1980s to the late 1990s, the North-South divide decreased significantly for both sexes. This was followed by a rise from 2000 to 2008.
Professor Iain Buchan said it was unclear why rates had fluctuated over the whole period. The rise in the rates coincided with a boom period for the economy and significant investment in northern cities.
Professor Iain Buchan said that the differences were not due to behavioural differences: "These differences are not because those in the north are not looking after themselves... this is because of social, economic and health care resources controlled by government. For example, there are fewer GPs in deprived areas."
The Department of Health said it was committed to reducing health inequalities: "We are also providing a ring-fenced public health budget, weighted towards the most deprived areas, to ensure resources are spent on preventative work, with incentives to improve the health of the poorest, the fastest."
However public health expert, Professor Alan Maryon-Davis said government cuts would worsen health inequalities: "Health care also depends very much on social care and voluntary support in the community. I'm afraid that, with the huge cuts in local authority budgets in places like Liverpool, Manchester and other parts of the North, the divide is only likely to widen even further."