Paramedics arrived at Heavy D’s Beverly Hills condo at about noon on Tuesday, after a neighboutr dialled 911.
The rapper was conscious and talking, but had collapsed after returning home from a shopping trip.
“There doesn’t appear to be any foul play,” police lieutenant Mark Rosen told the New York Daily News.
“We believe it was medically related.”
The man born Dwight Arrington Myers was suffering from pneumonia after a recent trip from Europe.
He was taken by ambulance to Cedars Sinai Medical Center, where he died at about 1pm. Autopsy results are forthcoming.
Heavy D found fame with his band The Boyz, scoring hits with such tracks as Now That We Found Love.
He appeared on Michael Jackson’s 1991 song Jam and recently performed at the singer’s tribute concert in Cardiff.
With The Boyz, he set the tone for New Jack Swing – sparse production, metallic drum loops and big R&B hooks – and paved the way for the likes of Bobby Brown and Blackstreet.
Three of his albums – Big Tyme (1989), Peaceful Journey (1991) and Nuttin’ but Love (1994) – went platinum in the US.
In the early 1990s, he duetted with the likes of Notorious BIG and Janet Jackson, cheekily branding the latter “a walking bank vault” on her hit single Alright.
His acting career took off in the early 2000s, with appearances on TV shows such as Law & Order: SVU and Boston Public.
He also made appearances in movies, with roles in The Cider House Rules and, most recently, alongside Ben Stiller and Eddie Murphy in the comedy Tower Heist.