In 1981 the band collaborated with musician David Byrne to produce a third full-length studio album. Due to alleged conflicts with Byrne over the album's musical direction, recording sessions for the album were aborted, prompting the band to release Mesopotamia (1982) as an extended play (EP); in 1991, Party Mix! and Mesopotamia, the latter of which had been remixed, were combined and released together on a single compact disc.
In 1983 the band released their fourth album Whammy!; this album brought the band into synthesizer and drum machine experimentation. The album entered the Billboard 200 chart in 1983, reaching number twenty-nine during the year. "Legal Tender" reached the Billboard Hot 100 chart, as well as the Billboard Hot Dance Club Play Singles chart alongside "Whammy Kiss" and "Song for a Future Generation". After initial pressings of Whammy! were released, copyright issues with Yoko Ono led to the song "Don't Worry" being removed and replaced on future pressings by "Moon 83", a remixed version of the track "There's a Moon in the Sky (Called the Moon)" from their debut album.
After taking a one-year absence from their musical careers in 1984 The B-52's regrouped in 1985 to record Bouncing off the Satellites, their fifth studio record, and in January of that year they performed in Brazil, at Rock in Rio; their largest crowd ever. During the recording, guitarist Wilson had been suffering from AIDS/HIV-related health complications. None of the other band members were aware of his illness.In an interview, fellow band member Kate Pierson stated that Wilson had kept his illness secret from his fellow band members because he "did not want anyone to worry about him or fuss about him." On October 12, 1985 Wilson died from the illness, at the age of 32.
With Cindy Wilson devastated by her brother's death, and her bandmates too being depressed about Ricky's passing, the band went into seclusion and did not tour to promote their album nor the group, prompting a hiatus from their musical careers. In 1987, they released a public service announcement in the style of The Beatles' Sgt Pepper's Lonely Hearts Club Band album cover on behalf of AMFAR (The Foundation for AIDS Research).
The B-52's hit "Love Shack" was ranked #40 on VH1's 100 Greatest Songs of the 80s.
The B-52's 1979 album The B-52's was ranked #152 on Rolling Stone magazine's 500 Greatest Albums of All Time.
The B-52's 1979 album The B-52's was ranked #99 on VH1's 100 Greatest Albums.
The B-52's's hit "Love Shack" was ranked #97 on Rolling Stone magazine and MTV's 100 Greatest Pop Songs.
The B-52's's hit "Rock Lobster" was ranked #99 on VH1's 100 Greatest Dance Songs.
The B-52's were ranked #47 on VH1's 100 Greatest Women of Rock & Roll.
The B-52's's music video "Love Shack" was ranked #35 on Rolling Stone magazine's The 100 Top Music Videos.