To define virologic and immunologic differences in patients with acute symptomatic and asymptomatic primary human immunodeficiency virus type 1 (HIV-1) infection, sequential plasma specimens were obtained longitudinally for 1–2 years postseroconversion from subjects with well-documented time of seroconversion. Thirteen of them had an acute symptomatic primary infection, eight subjects had asymptomatic primary infection and long-term follow-up, and 27 had asymptomatic seroconversion and short-term follow-up. Quantitative plasma HIV-1 RNA levels, CD4+ lymphocyte counts, and levels of antibodies to gp120, p66, p41, p31, p24, and p17 were measured. At the time of seroconversion, there was no significant difference in HIV-1 RNA levels and CD4+ counts between symptomatic (n= 13) and asymptomatic (n= 27) subjects. Subsequently, however, establishment of low levels of plasma HIV-1 RNA was seen significantly more frequently in asymptomatic (n= 8) than in symptomatic (n= 13) primary infection; this correlated with higher levels of some (anti-gp120 and anti-p31) anti-HIV-1 antibodies and a slower decline in CD4+ lymphocyte counts. These results indicate that immunologic control of viremia early after infection may be a critical determinant to subsequent clinical course of HIV-1 infection. They also suggest that persons with acute symptomatic primary infection may generally progress to having acquired immune deficiency syndrome (AIDS) more rapidly than people with low-grade symptoms or asymptomatic primary infection.