227 followed the lives of people in a middle-class apartment building, 227 Lexington Place (the numerical address from which the sitcom's name comes), in a Black neighborhood in Northeast, Washington, D.C. The show was centered around Mary Jenkins (Marla Gibbs), a nosy and tart-tongued but loving housewife. Her husband Lester Jenkins (Hal Williams) had his own construction company and their daughter Brenda (Regina King in her first television acting role) was boy-crazy yet smart and studious.
Also cast in 227 was Sandra Clark (Jackée Harry), Mary's younger neighbor who constantly bickered back and forth with her about their respective views on life. Although their relationship was antagonistic at first, Mary and Sandra became good friends as time went on. Also living in the building was Pearl Shay (Helen Martin), a feisty but kind-hearted busybody neighbor on the first floor who was known for snooping and had a sharp sense of humor. Pearl had a grandson named Calvin Dobbs (Curtis Baldwin), whom Brenda had a crush on and would finally date later in the series' run.
Rose Lee Holloway (Alaina Reed Hall) was Mary's level-headed best friend and often the voice of reason among 227's residents. She and Mary were often seen sitting on the front stoop of the building, exchanging rumors and gossip with Pearl adding sly commentary and humor from her front window. In the premiere episode, Rose became the unexpected landlady of the building after the building's stingy slumlord Mr. Calloway died. Rose stayed on as landlady until the fourth season and had a daughter named Tiffany Holloway (Kia Goodwin) who was Brenda's closest friend. However, Goodwin's mother was unhappy in California, so the child actor was released from her contract. Tiffany was written out of the series after the second season, although she was mentioned occasionally.
In the first season, both Helen Martin and Curtis Baldwin, who had only been recurring stars, appeared in nearly every episode. From season 2 onward, they were upped to series regulars.
By the time taping started on the third season in 1987, Jackée Harry, who had just won an Emmy for Outstanding Supporting Actress, changed her stage name to simply Jackée, which she used until 1994. In the fourth season, an 11-year-old child prodigy named Alexandria DeWitt () became the Jenkins' house guest. Vaughn received her role after she appeared on Star Search and declared to host Ed McMahon that her favorite show was 227. However, Alexandria left during Calvin's graduation episode near the end of season four to reunite with her father, who, after completing his archaeological dig in the Amazon, had moved to London to catalogue his items.