The song's vocals are performed primarily by Lou Reed, with John Cale and Sterling Morrison performing backing vocals. The song, much like "I'm Waiting for the Man", features a pounding rock-and-roll Barrelhouse-style piano vamp. The song is about the sensations produced by intravenous injection of methamphetamine and features a heavily distorted electric bass outro played by John Cale over a single chord. This bass solo purportedly mimics the throbbing, ear-ringing effects experienced during the methamphetamine "rush."
"White Light/White Heat" was released in 1968 as a single with the B-side "Here She Comes Now". "White Light/White Heat" was also a staple of the Velvet Underground's live performances from 1967 on. The tune appears on numerous live bootleg albums, and the nearly nine minute version included on the group's posthumous 1969 Live double LP is one of the album's centerpieces.
Reed also recorded a live version of the song in 1974, which is featured on his Rock 'n' Roll Animal and Greatest Hits albums.
Two traditional-music influenced versions of the song were included on the soundtrack to the 2012 film Lawless, one by The Bootleggers featuring Mark Lanegan and one by bluegrass legend Ralph Stanley.
Bowie, a long-time Velvets fan, had been performing "White Light/White Heat" since 1971. (His album of that year, Hunky Dory, features a credit to the song for having inspired Bowie's "Queen Bitch"). It had featured throughout the Ziggy Stardust tour (including a performance with Lou Reed on July 8, 1972), been recorded by Bowie for two BBC sessions, and been slated for inclusion on Pinups (the backing track from this session was later recorded as a solo version by Mick Ronson in 1975). Despite this, the Ziggy Stardust – The Motion Picture project would be the first time the song had been issued on a Bowie record, and as such it was released as a single.
With Bowie at the peak of his global stardom thanks to Let's Dance, "White Light/White Heat" was considered an unusual turn for the pop audience he had attracted, and reached only #46 in the UK. The song has continued to feature in Bowie’s live repertoire.