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1972: Three people—an Arizona peace activist named Cleve Jones, an African-American sailor Ken Jones in Vietnam, and a Boston women's activist Roma Guy—all move to San Francisco to join the nascent gay community.

Roma helps take a stand against the National Organization for Women's attempts to purge lesbians from their ranks. Ken comes to accept—and fight for—his sexuality. After struggling to find San Francisco less welcoming than he'd hoped, Cleve hears of a New Yorker, Harvey Milk, running for election to the San Francisco Board of Supervisors.

1978–79: Roma sees the establishment of The Women's Building. Harvey Milk runs for the Board of Supervisors against a backdrop of Anita Bryant's Moral Majority and John Briggs's statewide initiative to ban gay people and allies from working with children.

1981: A new disease, initially named gay-related immune deficiency, starts spreading among gay men and drug users in San Francisco. Roma and Diane start a family.

1992: A decade after the advent of the AIDS Crisis, Cleve (now played by Guy Pearce) unveils the NAMES Project AIDS Memorial Quilt in Washington, D.C., and visits ACT UP in New York as they fight for early clinical trials of new drugs. Ken (now played by Michael K. Williams) finds his life turned upside down when Richard dies of AIDS. Roma and Diane (now played by Mary-Louise Parker and Rachel Griffiths) work with Tom Ammiano to see Carole Migden elected to the Board of Supervisors—and find out he's the biological father of their daughter Annie.

2008: As Barack Obama is elected president, California Proposition 8 revokes California's recently-acquired marriage equality, starting Cleve to help organise the National Equality March on Washington, D.C., and advocate for equal rights. Roma, Diane and Tom become grandparents and advocate for citywide universal healthcare in San Francisco. Ken is baptised, but finds some churches are less welcoming than others.

2009–13: Cleve takes the battle against Prop 8 through the federal courts all the way to the Supreme Court. Ken works with Cecilia Chung to get support for his church. Roma and Diane decide to get married if the Supreme Court allows it.