England's independent exam regulator is to ask experts to discuss more evidence that it is harder to get top exam grades in some subjects than others.
Durham University researchers say the hardest A-level is physics - along with general studies, though that is usually disregarded by universities.
At GCSE level, languages generally were harder than sciences, while citizenship was harder than physics.
A head teachers' leader has called for the exams to be brought into line.
The new regulatory body, Ofqual, said it welcomed Durham's comprehensive study of the work to date on making judgements about standards between different subjects.
"There is currently no expert consensus as to what statistical outcomes like these mean in terms of grading standards between different subjects," a spokesman said.
"Because it is vital that exams are seen to be fair for all students, Ofqual will be holding a seminar in the autumn to bring together those working on different approaches to comparability between subjects to discuss how work in this area might be taken forward."
The Durham researchers compared data on nearly a million GCSE and A-level candidates and reviewed 28 different studies of cross-subject comparison conducted in the UK since 1970.
Their report was compiled for Score - a science community lobby group.
The researchers discuss the various methods that have been tried to determine the relative difficulty of subjects, then applied five different methods to the data.
On average subjects such as physics, chemistry and biology at A-level were a whole grade harder than drama, sociology or media studies, and three-quarters of a grade harder than English, RE or business studies.
Someone who took history rather than film studies could expect to score a whole grade less, the report said.
Lead author Dr Robert Coe said: "I can't see how anyone could claim that all A-levels are equally difficult.
"If universities and employers treat all grades as equivalent they will select the wrong applicants. A student with a grade C in biology will generally be more able than one with a B in sociology, for example.
"The current system provides a disincentive to schools to promote take-up of sciences while league tables treat all subjects as equal."
There are no league tables in Scotland - where a previous study had identified differences in the difficulty of Highers subjects, the report notes.
Dr Coe said this was accepted there much more openly and people perhaps were given credit for studying harder subjects.
Earlier this year England's exams regulator the Qualifications and Curriculum Authority issued a report which also said some exams may be harder than others - but concluded they were "broadly in line".
Schools Minister Jim Knight said Ofqual had been set up precisely to maintain rigorous standards and control the exam and qualifications system tightly.
They would "continue to ensure public confidence in the standards of qualifications and tests".
Shadow Schools Minister Nick Gibb said: "We need to be sure that weaker schools, particularly those in poorer areas, are not pushing children to take subjects that boost schools' league table positions but are regarded in the real world as softer or less valuable.
"It is a cruel trick to play on children who may then find they cannot go to the top universities or get the jobs they want because of the subjects they have taken."
John Dunford of the Association of School and College Leaders has been saying for some years that schools and universities know some subjects are harder than others.
He said: "Examinations need to be brought in line as the current situation is creating a disincentive for students to study languages, maths and the physical sciences, which the country and the economy desperately need."