A window of opportunity for immune responses to extinguish HIV-1 exists from the moment of transmission through establishment of the latent pool of HIV-1-infected cells. A critical time to study the initial immune responses to the transmitted/founder virus is the eclipse phase of HIV-1 infection (time from transmission to the first appearance of plasma virus). To probe B cell responses immediately following HIV-1 transmission, we determined envelope-specific antibody responses to autologous and consensus Env in subjects for whom frequent plasma samples were available immediately before, during, and after HIV-1 plasma viral load ramp-up in acute infection, and modeled antibody effect on the kinetics of plasma viremia. The first detectable B cell response was in the form of antibody–virion immune complexes 8 days after first plasma virus detection (100 copies/mL), whereas the first free plasma anti-HIV-1 antibody was to gp41 and appeared 13 days after the appearance of plasma virus. In contrast, envelope gp120-specific antibodies were delayed an additional 14 days. Thus, the host–pathogen interactions occurring during and immediately after transmission result in a delay in recognition of gp120 by host B cells until after the latent pool of infected cells is likely established. We also found rheumatoid factor in approximately 30% of subjects, thus likely indicating polyclonal B cell activation of CD5⁺ B cells, which produce rheumatoid factor auto-antibodies. Also of interest is the heterogeneity in the pattern of immunoglobulin (Ig) class-switching following HIV-1 transmission. Mathematical modeling of the earliest viral dynamics with the initial anti-gp41 IgG and IgM antibody responses demonstrated that the first IgM and IgG antibodies induced by transmitted HIV-1 had little effect on reducing acute phase viremia at the timing and magnitude that they occur in natural infection.