Researchers found that a 50-minute call led to a localised increase in brain activity of 7%, but they said there was no evidence to suggest the rise was harmful.
To rule out the variation in brain activity that would be expected when someone listens to a call normally, changes in brain were monitored while the phone was taking a call but was muted.
The team, led by Nora Volkow, director of the National Institute on Drug Abuse in Maryland, found that brain activity rose in line with the strength of the electromagnetic field to which the particular brain region was exposed.
Mobile phones use radio waves to send and receive calls and these produce small electromagnetic fields that can be absorbed by the head and brain.
"Although we cannot determine the clinical significance, our results give evidence that the human brain is sensitive to the effects of radio-frequency electromagnetic fields from acute cellphone exposures," Dr Volkow said. The study appears in the Journal of the American Medical Association.
The dramatic rise in mobile phone use around the world has prompted concerns about possible harmful effects, including brain tumours. Last year, the much-delayed Interphone report found no hard evidence that mobile phones increase the risk of cancer, but the issue remains unresolved.
In the new study, 47 volunteers were given two brain scans, each on different days. The scans, which used a technique called positron emission tomography (PET), were designed to monitor changes in the way the brain metabolised glucose, the fuel it needs to function.
Before being scanned, the volunteers had a mobile phone positioned against each ear. In one scan, both phones were switched off. But in the other scan, the phone on the right ear was switched on, muted, and set to receive a lengthy recorded message. The volunteers were not told which scan was which.
When they compared scans taken in these two different scenarios, Volkow's team discovered a pattern of increased brain activity in the right orbitofrontal cortex and the lower parts of the right superior temporal gyrus. In these areas of the brain, glucose metabolism rose from 33.3 to 35.7 micromoles of glucose per 100g each minute.
Brain activity can rise a lot more than this when a person simply looks at images on a screen. In 2006, Andrei Vlassenko at Washington University School of Medicine reported that viewing images could boost brain activity by between six and 51%. Vokow said these rises were caused by thinking about images, while mobile phones appeared to boost activity "artificially".
She said it was unclear how mobile phone radiation might affect brain metabolism and added that more studies were needed to investigate whether the effects could be harmful to health. Since completing the study she has started using an earpiece with her mobile phone, a move she described as "conservative, not paranoid".
However, if increases in brain activity caused by mobile phone use are found to be harmless, Volkow said, the phenomenon could be exploited to stimulate patients who have underactive brain areas.