In the opening chapter of Of Mice and Men, we are introduced to two main characters, George Milton and Lennie Small, whose contrasting physical appearances symbolize their unique personalities and roles in their relationship. George is described as a small, wiry man with sharp features, while Lennie is a large man with a robust build, yet he possesses a mental disability that renders him childlike and dependent on George for guidance and protection.

The chapter sets the scene near the Salinas River in California, where the pair has just arrived after escaping from their previous job in Weed. As they journey, George reveals their dream of owning a piece of land, a vision that represents hope and stability amidst the uncertainty of their nomadic lives as migrant workers. This dream is characterized by George's detailed descriptions of the land they wish to buy, including a small house, a garden, and the ability to live off the fat of the land. For Lennie, the dream is particularly appealing because it includes the prospect of tending rabbits, showcasing his innocence and simplistic desires.

Their conversation reveals the dynamics of their relationship; George often takes on the role of caretaker, while Lennie is portrayed as innocent yet prone to mishaps due to his lack of understanding of social boundaries and his own strength. Despite his occasional frustration with Lennie's behavior, George's affection for him is evident, and he often reassures Lennie about their dream, emphasizing loyalty and companionship as key themes.

As they set up camp for the night, George instructs Lennie to stay quiet when they reach the ranch the following day and warns him against causing trouble, highlighting the precarious nature of their situation. The reader learns about Lennie’s past mistakes, particularly in Weed, where he was accused of attempted assault due to his unintentional actions, showcasing the challenges they face due to Lennie's condition.

The chapter concludes with the two men settling down to sleep, signifying a moment of peace before they face the harsh realities of their lives as itinerant workers. This opening sets the tone for the novella, establishing themes of friendship, dreams, and the struggles of individuals during the Great Depression, while foreshadowing the difficulties that George and Lennie will encounter as they strive to achieve their aspirations.