Amateur video shows people on the street running for cover as constant sounds of gunfire surrounded the governor's house in Daraa in the country's south.
Security forces are reported to have opened fire with rubber bullets and live rounds to disperse stone-throwing protesters during demonstrations in Daraa, Homs and Harasta.
Early reports indicate at least 22 protesters were killed - 17 in Daraa, two in Homs and three in Harasta.
Syrian TV says 19 members of security forces were also killed and 75 wounded by "armed groups" in Daraa.
An activist said the situation in the city, about 60 miles (100km) south of the capital, Damascus, was "very tense".
"Thousands of demonstrators leaving from three mosques marched to the courthouse but security forces dressed in civilian clothing fired tear gas to disperse them," he said.
"Demonstrators threw stones and clashes ensued."
He added that protesters angered by the deaths set fire to the ruling Baath party's headquarters in the city.
And in northern Syria, thousands of people are also understood to have marched in five towns including Hassake and Ammuda, calling for an end to emergency rule and the release of prisoners, another activist said.
The rallies came a day after Syrian president Bashar al Assad granted citizenship to tens of thousands of Kurds who had been denied nationality for nearly half a century because of a controversial census.
Following the latest clashes and subsequent deaths, Foreign Secretary William Hague has called for the Syrian government to respect the right of peaceful protest.
"I am deeply concerned by the continuing deaths and violence in Syria, including in Daraa earlier today," he said in a statement.
"I condemn the killing of demonstrators by the Syrian security forces.
"Political reforms must be brought forward and implemented without delay."
Since March 15, when dozens marched in Damascus in what activists called the first overt protest in Syria since a state of emergency was declared in 1963, violent demonstrations and marches have intensified in the country.
On April 1, the International Federation for Human Rights (IFHR) put the death toll from the Syrian conflict at 123.