In Leisure Suit Larry 6, there is a scene where Larry tries to seduce Shablee on the beach. As they are about to have sex, he finds out she is a trans woman and has a very transphobic reaction which can be seen at the end of the video below.

LGBTQ  references in this game series: 

Leisure Suit Larry (1987): Comedian’s jokes

Leisure Suit Larry 3 (1989): Bobbi and Kalalau; Suzi; Cross-dressing; Lesbian Cannibals

Leisure Suit Larry 5 (1991): Sign in airport

Leisure Suit Larry 6 (1993): Gary; Gay Game Over; Cavaricchi; Shablee; Larry’s Reaction to Shablee

Leisure Suit Larry: Magna Cum Laude (2004): Spartacus gay bar, Ione, Luba

Leisure Suit Larry: Box Office Bust (2009): Damone LaCoque

Citations:

1. Shablee. (n.d.). Retrieved from http://leisuresuitlarry.wikia.com/wiki/Shablee
2. Sierra Chest. (2009, December 21). Leisure Suit Larry 6 (part 11/25): Larry and Shablee on the beach. YouTube. https://www.youtube.com/watch?v=3c_U73BagT4