The magnitude-7.3 quake's epicenter was northwest of the capital city of Kathmandu, near the Chinese border. Shaking was felt throughout Nepal and neighboring Tibet.
Help Nepal: Support quake relief and recovery efforts
It was followed by a dozen large aftershocks, the largest of which was a magnitude-6.3.
Nepal's Home Ministry says at least 42 people have died and over 1,000 others have been injured.
Rescue teams in Nepal are again digging through the debris, searching for survivors.
ABC7 SPECIAL REPORT: Experiencing 7.3 Nepal quake
Crowds were screaming and rushing to safety as the powerful quake hit around 1 p.m. local time, just after midnight our time.
ABC7 News reporter Sergio Quintana is the only Bay Area reporter in Kathmandu. He says he ran from his hotel room without his shoes on and watched as panicked residents poured into the streets.
Just had a very strong quake. I'm safe. We all ran out into the hotel's patio. It lasted about 40 seconds. pic.twitter.com/ZLMYRQaeVI— Sergio Quintana (@svqjournalist) May 12, 2015
"Thousands of people streamed out of the downtown Tamal District, terrified that some of the buildings were going to collapse on them. Lots of people also immediately shut down their businesses and went home," Quintana said.
People left work after quake. Many were crying and worried buildings would collapse on them. pic.twitter.com/3hbIqqNW5J— Sergio Quintana (@svqjournalist) May 12, 2015
Quintana tweeted videos shortly after the quake hit.
Downtown Kathmandu seconds after the 7.3 quake. People fled from the congested market area. pic.twitter.com/yMtyHVdNgo— Sergio Quintana (@svqjournalist) May 12, 2015
There is a sense of panic in the dense downtown area of Kathmandu because of this latest quake. pic.twitter.com/VGOCWSek5b— Sergio Quintana (@svqjournalist) May 12, 2015
He is in Nepal following a group of aid workers on a recovery mission.
The earthquake rocks a country struggling to recover from a deadly magnitude-7.8 earthquake that shook the region just 17 days ago.
Tuesday's shaking was reported as far away as New Delhi, India.
PHOTOS: Second major earthquake strikes Nepal
"The cars were shaking, the buildings were swaying. I think one of the most shocking things was how long the earthquake went on for," Canadian Red Cross' James Shaw said.
Some buildings crumbled and an ancient temple collapsed as workers inside ran for their lives.
The quake also triggered a rockslide in the mountains. Homes sit just feet away as boulders barreled down the hill.
Nepalese, many traumatized by April's quake, now have to deal with the aftershocks.
These are very large aftershocks. Five in a row were greater than 5.0. One measured nearly three times stronger than the one that hit Napa last summer.
The relief and recovery efforts in Nepal will likely need even more help now. If you would like to donate, you can text NEPAL to 90999 to contribute $10 or call 1-800-RED-CROSS.
Click here to find out how you can help the victims in Nepal, and click here for full coverage on the devastating quake.
ABC7 News reporter Sergio Quintana is in Nepal. You can see his Twitter updates here.