The greater the number of special needs pupils a school admits, the worse it tends to perform in tests, government research shows.
But the study by Manchester and Newcastle universities concluded that there was not necessarily a "causal link" between inclusion and poorer test results. Instead researchers suggested that other factors might be responsible.
Schools with higher levels of inclusion tended to serve more disadvantaged areas, they said, and the results of schools which had the same proportion of special needs students varied greatly.
The study for the Department for Education and Skills follows fears that the government drive to include special needs pupils in mainstream schools may be damaging other pupils' education.
The researchers analysed information from the national pupil database. They found a small but significant link between inclusion and lower results.
At key stage 4, where pupils get an average of 36 points, schools lost half a point for every 1 per cent of special needs pupils on roll.
The report said its findings "call into question some of the more optimistic advocacy of inclusion which suggests that, as schools educate more pupils with higher levels of special needs, they will become more effective at educating all of their pupils".
The researchers polled 180 teachers and found that more than a third felt the biggest problem with inclusion was that special needs pupils disrupted other children's learning.
One teacher said: "When a class has one or more pupils with a high level of special needs, this dilutes the provision for other pupils and I feel that they can suffer."
However, the report stressed that teachers and pupils felt inclusion had improved their social skills and understanding.
Nearly all of the teachers surveyed said they supported the principle of inclusion and felt it worked in their schools.
A primary head said he had been surprised to see a group of children at his school sniggering at a pupil with cerebral palsy. He then realised they had all joined recently from a less inclusive school so were not accustomed to students with special needs.
Steve Sinnott, general secretary of the National Union of Teachers, said:
"It's no surprise that the academic achievements of a school are affected if it is in an area of deprivation and has a high proportion of special needs pupils. This underlines the complete inadequacy of league tables.
Integration has many benefits for schools, but they go beyond those which can be easily measured by tests."
Mike Collins, head of education services for the National Autistic Society, said he had attended a lesson where the teacher had asked a child with Asperger's to take the class because of his knowledge of the planets.
"Good teaching for pupils with autism is good teaching for all pupils," he said. "They all benefit from structure and from clear language."
Inclusion and pupil achievement is at www.dfes.gov.uk